Studies in Ipamorelin for Muscle Growth and Bone Density

Studies in Ipamorelin for Muscle Growth and Bone Density

Ipamorelin, also known as NNC 26-0161, is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2. Researchers suggest it may induce a peak in growth hormone (GH) synthesis by the pituitary gland via activating the growth hormone secretagogue receptors (GHS-Rs). In this respect, Ipamorelin is classified as a growth hormone secretagogue (GHS). It appears mimic the hunger hormone Ghrelin, which is considered a natural activator of the GHS-Rs.

Ipamorelin peptide appears to differentiate itself from other GHSs as a potentially more selective option that elevates GH levels without increasing other pituitary hormones, such as prolactin. Studies are still underway with this peptide within the context of postoperative ileus and speeding up the recovery of gastrointestinal function following damage.

 

Research

 

Ipamorelin and Growth Hormonse Synthesis

Studies suggest that Ipamorelin may be a highly selective growth hormone secretagogue, which may be capable of increasing GH levels in animals by activating the GHS-R receptors.[1,2]

Research studies report that the effect may occur relatively quickly – as soon as 40 minutes after exposure, there appeared to be a peak in GH levels. Increasing GH levels may potentially have numerous potential impacts, such as preserving muscle and lean body mass, increasing energy levels, improving bone mineral density, and more. [3]

 

Ipamorelin and Gastrointestinal Functions

Ipamorelin has been studied for its potential to alleviate delayed gastric emptying and post-surgical ileus in animals. In rodents, the peptide may significantly accelerate the rate of gastric emptying through stimulating gastric contractility.[4] The route via which the peptide may act appears to be by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons. The researchers reported that “Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%.

 

Ipamorelin and Appetite, Weight

Existing research suggests that Ipamorelin may increase appetite, reduce weight loss in the context of research studies in wasting disorders. This hypothesis is based on animal study findings. According to the researchers, these hypotheses are due to the apparent appetite-increasing characteristics of Ipamorelin.[5] The peptide appears to activate the receptors of the hunger hormone, which in turn may result in an increased food intake.

On the other hand, any growth hormone-increasing potential of Ipamorelin may also help reduce weight loss, especially protein loss. Studies posit that Ipamorelin may reduce muscle wasting in cortisol-exposed animals and help maintain a positive nitrogen balance.[6] The researchers conclude that “Accelerated nitrogen wasting in the liver and other organs caused by prednisolone [exposure] was counteracted by [influence] with either GH or its secretagogue Ipamorelin.

Another trial observes that Ipamorelin appears to negate the GH-inhibiting action of glucocorticoids in tested animals.[7] Animal studies suggest that Ipamorelin may also stimulate insulin secretion, another anabolic hormone that can help reduce muscle loss in wasting disorders.[8]

 

Ipamorelin and Bone

Growth hormones are considered a factor in maintaining optimal bone mineral density. Animal studies suggest that thanks to Ipamorelin’s alleged action on growth hormone synthesis and body weight, it may help maintain or even increase bone mass. One study on thirteen-week-old female Sprague-Dawley rats suggested that Ipamorelin exposure appeared to significantly increase bone mineral content after 12 weeks.[9] The increase was measured via a DEXA (dual-energy X-ray absorptiometry) scan and was significantly higher than the placebo group.

Another animal trial on rats treated with glucocorticoids reported that Ipamorelin has the potential to completely negate bone loss induced by glucocorticoids.[10] The scientists report that the periosteal bone formation rate increased four-fold in animals exposed to glucocorticoids and Ipamorelin in combination, compared with the group that received glucocorticoids alone.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References


  1. Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822.
  2. Gobburu JV, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999 Sep;16(9):1412-6. doi: 10.1023/a:1018955126402. PMID: 10496658.
  3. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014 Dec;29(12):1527-34. doi: 10.1007/s00384-014-2030-8. Epub 2014 Oct 21. PMID: 25331030.
  4. Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. J Exp Pharmacol. 2012 Oct 19;4:149-55. doi: 10.2147/JEP.S35396. PMID: 27186127; PMCID: PMC4863553.
  5. Lall S, Tung LY, Ohlsson C, Jansson JO, Dickson SL. Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochem Biophys Res Commun. 2001 Jan 12;280(1):132-8. doi: 10.1006/bbrc.2000.4065. PMID: 11162489.
  6. Aagaard NK, Grøfte T, Greisen J, Malmlöf K, Johansen PB, Grønbaek H, Ørskov H, Tygstrup N, Vilstrup H. Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth Horm IGF Res. 2009 Oct;19(5):426-31. doi: 10.1016/j.ghir.2009.01.001. Epub 2009 Feb 23. PMID: 19231263.
  7. Malmlöf K, Johansen PB, Haahr PM, Wilken M, Oxlund H. Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats. Growth Horm IGF Res. 1999 Dec;9(6):445-50. doi: 10.1054/ghir.1999.0128. PMID: 10629165.
  8. Adeghate E, Ponery AS. Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats. Neuro Endocrinol Lett. 2004 Dec;25(6):403-6. PMID: 15665799.
  9. Svensson J, Lall S, Dickson SL, Bengtsson BA, Rømer J, Ahnfelt-Rønne I, Ohlsson C, Jansson JO. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. J Endocrinol. 2000 Jun;165(3):569-77. doi: 10.1677/joe.0.1650569. PMID: 10828840.
  10. Andersen NB, Malmlöf K, Johansen PB, Andreassen TT, Ørtoft G, Oxlund H. The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Horm IGF Res. 2001 Oct;11(5):266-72. doi: 10.1054/ghir.2001.0239. PMID: 11735244
Research in BPC-157 and The Digestive and Nervous Systems

Research in BPC-157 and The Digestive and Nervous Systems

BPC-157 is a pentadecapeptide made of 15 amino acids and bears the sequence Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, and a molecular formula of C62H98N16O22. This is a fully synthetic peptide with a sequence not known to occur in nature. However, it is often termed a “gut peptide,” as it is suggested to have similar structure and properties to other gastroprotective peptides found in gastric juice.

According to the patent, the peptide’s production is fully synthetic and derived from various organic and inorganic bases. BPC stands for ‘Body Protection Compound.’ It appears to be relatively stable in stomach acid compared to other peptides.

Animal studies indicate the peptide’s potential to modulate the healing of various tissues, including tendons, joints, nerves, the intestinal tract, and skin. BPC-157 likely works via various pathways, including anti-inflammatory action, modulated nitric oxide synthesis, increased growth factor synthesis, and activation of cells involved in tissue repair.

 

Research

 

BPC-157 Peptide and the Digestive System

BPC-157 peptide is under investigation for its potential to protect against and treat ulcers in the gastrointestinal system. Animal studies suggest that the peptide has significant protective effects against compounds which are known to cause stomach ulcers.[1][2] Sikiric et al. report that “superior protection against different gastrointestinal and liver lesions and anti-inflammatory and analgesic activities were noted for pentadecapeptide BPC.” Researchers also suggest that this protective potential is likely related to the action of BPC-157 peptide on the alpha-adrenergic (e.g., catecholamine release) and dopaminergic (central) systems. Blocking the alpha-adrenergic or dopamine receptors may reduce the effectiveness of BPC-157 against ulcerations.

The peptide may also work by stimulating the synthesis of growth factors in the intestinal cells that cover the digestive system. Another laboratory study reports that BPC-157 peptide has also been suggested to stimulate the mRNA of the growth factor EGR-1.[3] As a result, experiments in rats report that BPC-157 peptide speeds up the healing of surgical injuries in the gastrointestinal system, specifically esophagogastric anastomosis healing.[4] Animal models with short-bowel syndrome also report that the peptide may help prevent weight loss and increase the ability of the bowels to absorb nutrients.[5,6] The researchers report constant weight gain and increased villus height, crypt depth, and muscle thickness of the small intestines. Furthermore, the scientists report that “BPC 157 completely ameliorated symptoms in massive intestinal resection.” Because of its interactions with various neurotransmitters, scientists have also investigated its effects on serotonin production. According to preliminary research BPC-157 may exert beneficial action on serotonin synthesis.[7]

 

BPC-157 Peptide and the Nervous System

Rat studies report that BPC-175 may significantly increase serotonin synthesis in several brain regions, including the “substantia nigra reticulata and medial anterior olfactory nucleus,” taking only 40 minutes for BPC-157 to exert these effects.[8]  One study in rats reported that BPC-157 peptide exhibited possible antidepressant characteristics when the animals were exposed to acute or chronic stress.[9]

BPC-157 peptide may also help ameliorate damage to the brain through various chemicals. According to one experiment which used cuprizone to induce brain damage and nerve demyelination like those observed in multiple sclerosis (MS), BPC-157 had potential protective action.[10] BPC-157 peptide appeared to have reduced the number of damaged cells in numerous brain regions, including the hippocampus. Another study that used a toxin to induce damage, like what is seen in Parkinson’s Disease in rodents, reports that BPC-157 may exerts protective action.[11]

 

BPC-157 Peptide and Skin, Bones, and Joints

BPC-157 peptide may have action that extend beyond the gastrointestinal and nervous systems, such as stimulating the repair of the skin tissues, bones, joints, tendons, and other tissues. These possible actions could be due to the potential of BPC-157 peptide to stimulate the formation of new blood vessels. By stimulating angiogenesis, BPC-157 may increase the supply of tissues with nutrients and growth factors.

According to one study in rats with injured limbs, the scientists noted an increase in VEGFR2 expression, which was much more significant compared to controls.[12] Hsieh et al. also noted that “BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia.”

In tendon and joint injuries, BPC-157 peptide may also speed up the recovery of connective tissues by upregulating fibroblast function. Experiments note that BPC-157 may allow tendon fibroblasts to grow and spread faster.[13] The researchers note that the effect was present only when the fibroblasts were replanted. Another experiment also reported increased wound healing potential in rats after injuries induced via surgical cuts. The researchers hypothesized that BPC-157 peptide might significantly increase the rate of injury healing when compared to the control.[14]

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References


  1. Luetic K, Sucic M, Vlainic J, Halle ZB, Strinic D, Vidovic T, Luetic F, Marusic M, Gulic S, Pavelic TT, Kokot A, Seiwerth RS, Drmic D, Batelja L, Seiwerth S, Sikiric P. Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157. Inflammopharmacology. 2017 Apr;25(2):255-264. doi: 10.1007/s10787-017-0330-7. Epub 2017 Mar 2. PMID: 28255738.
  2. Sikirić P, Mazul B, Seiwerth S, Grabarević Z, Rucman R, Petek M, Jagić V, Turković B, Rotkvić I, Mise S, Zoricić I, Jurina L, Konjevoda P, Hanzevacki M, Gjurasin M, Separović J, Ljubanović D, Artuković B, Bratulić M, Tisljar M, Miklić P, Sumajstorcić J. Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress. Dig Dis Sci. 1997 Mar;42(3):661-71. doi: 10.1023/a:1018880000644. PMID: 9073154.
  3. Tkalcević VI, Cuzić S, Brajsa K, Mildner B, Bokulić A, Situm K, Perović D, Glojnarić I, Parnham MJ. Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression. Eur J Pharmacol. 2007 Sep 10;570(1-3):212-21. doi: 10.1016/j.ejphar.2007.05.072. Epub 2007 Jun 16. PMID: 17628536.
  4. Djakovic Z, Djakovic I, Cesarec V, Madzarac G, Becejac T, Zukanovic G, Drmic D, Batelja L, Zenko Sever A, Kolenc D, Pajtak A, Knez N, Japjec M, Luetic K, Stancic-Rokotov D, Seiwerth S, Sikiric P. Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME. World J Gastroenterol. 2016 Nov 7;22(41):9127-9140. doi: 10.3748/wjg.v22.i41.9127. PMID: 27895400; PMCID: PMC5107594.
  5. Sever M, Klicek R, Radic B, Brcic L, Zoricic I, Drmic D, Ivica M, Barisic I, Ilic S, Berkopic L, Blagaic AB, Coric M, Kolenc D, Vrcic H, Anic T, Seiwerth S, Sikiric P. Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats. Dig Dis Sci. 2009 Oct;54(10):2070-83. doi: 10.1007/s10620-008-0598-y. Epub 2008 Dec 18. PMID: 19093208.
  6. Lojo N, Rasic Z, Zenko Sever A, Kolenc D, Vukusic D, Drmic D, Zoricic I, Sever M, Seiwerth S, Sikiric P. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats. PLoS One. 2016 Sep 14;11(9):e0162590. doi: 10.1371/journal.pone.0162590. PMID: 27627764; PMCID: PMC5023193.
  7. Sikiric P, Seiwerth S, Rucman R, Kolenc D, Vuletic LB, Drmic D, Grgic T, Strbe S, Zukanovic G, Crvenkovic D, Madzarac G, Rukavina I, Sucic M, Baric M, Starcevic N, Krstonijevic Z, Bencic ML, Filipcic I, Rokotov DS, Vlainic J. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Curr Neuropharmacol. 2016;14(8):857-865. doi: 10.2174/1570159×13666160502153022. PMID: 27138887; PMCID: PMC5333585.
  8. Tohyama Y, Sikirić P, Diksic M. Effects of pentadecapeptide BPC157 on regional serotonin synthesis in the rat brain: alpha-methyl-L-tryptophan autoradiographic measurements. Life Sci. 2004 Dec 3;76(3):345-57. doi: 10.1016/j.lfs.2004.08.010. PMID: 15531385.
  9. Sikiric P, Separovic J, Buljat G, Anic T, Stancic-Rokotov D, Mikus D, Marovic A, Prkacin I, Duplancic B, Zoricic I, Aralica G, Lovric-Bencic M, Ziger T, Perovic D, Rotkvic I, Mise S, Hanzevacki M, Hahn V, Seiwerth S, Turkovic B, Grabarevic Z, Petek M, Rucman R. The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt’s test and chronic unpredictable stress in rats. A comparison with antidepressants. J Physiol Paris. 2000 Mar-Apr;94(2):99-104. doi: 10.1016/s0928-4257(00)00148-0. PMID: 10791689.
  10. Klicek R, Kolenc D, Suran J, Drmic D, Brcic L, Aralica G, Sever M, Holjevac J, Radic B, Turudic T, Kokot A, Patrlj L, Rucman R, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability. J Physiol Pharmacol. 2013 Oct;64(5):597-612. PMID: 24304574.
  11. Sikiric P, Marovic A, Matoz W, Anic T, Buljat G, Mikus D, Stancic-Rokotov D, Separovic J, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Ziger T, Sebecic B, Zoricic I, Turkovic B, Aralica G, Perovic D, Duplancic B, Lovric-Bencic M, Rotkvic I, Mise S, Jagic V, Hahn V. A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson’s disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine. J Physiol Paris. 1999 Dec;93(6):505-12. doi: 10.1016/s0928-4257(99)00119-9. PMID: 10672997.
  12. Hsieh MJ, Liu HT, Wang CN, Huang HY, Lin Y, Ko YS, Wang JS, Chang VH, Pang JS. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med (Berl). 2017 Mar;95(3):323-333. doi: 10.1007/s00109-016-1488-y. Epub 2016 Nov 15. PMID: 27847966.
  13. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol (1985). 2011 Mar;110(3):774-80. doi: 10.1152/japplphysiol.00945.2010. Epub 2010 Oct 28. PMID: 21030672.
  14. Staresinic M, Sebecic B, Patrlj L, Jadrijevic S, Suknaic S, Perovic D, Aralica G, Zarkovic N, Borovic S, Srdjak M, Hajdarevic K, Kopljar M, Batelja L, Boban-Blagaic A, Turcic I, Anic T, Seiwerth S, Sikiric P. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res. 2003 Nov;21(6):976-83. doi: 10.1016/S0736-0266(03)00110-4. PMID: 14554208.
IGF-1 LR3 Peptides and Tissue Growth

IGF-1 LR3 Peptides and Tissue Growth

 
Scientists have created IGF-1 LR3 peptides by modifying the amino acid sequence of IGF-1. The new peptide has similar potential but possibly higher potency and improved stability. The LR3 in the name describes the two modifications to the IGF-1 molecule. Long R3 IGF-1, or IGF-1 LR3, is an analog of insulin-like growth factor 1 (IGF-1). IGF-1 is an anabolic peptide hormone naturally produced. Primarily, it is considered a mediator of the anabolic effects of growth hormone (HGH). Growth hormone appears to stimulate the production of IGF-1. The IGF-1 produced in the liver is released in the bloodstream and exerts anabolic effects, while the IGF-1 produced in all other tissues acts locally to stimulate growth. The first is R3 which describes the replacement of the 3rd amino acid in IGF-1 with arginine. Scientists ascribed an additional 13 amino acids to the N-terminus of the R3 IGF-1 molecule, turning it into Long R3 IGF-1. IGF-1 LR3 is an experimental peptide with potential anabolic and mitogenic effects.

 

IGF-1 LR3

Scientists developed IGF-1 analogs such as IGF-1 LR3 primarily for experiments to stimulate cell growth. IGF-1 and its analogs appear to be highly anabolic towards actively proliferating cells. They may speed up cell replication, ultimately shortening the time required to create a cell culture and use it to conduct laboratory studies.

IGF-1 LR3 works by activating IGF-1 receptors in most animal cells. Activating these anabolic receptors increases protein synthesis and tissue growth.  IGF-1 LR3 peptide appears to bind to a much lesser degree to IGF-1 proteins than other available analogs. Therefore, its affinity to the anabolic IGF-1 receptors may be much higher, and animal studies show that continuous exposure to IGF-1 LR3 leads to a 2-fold higher anabolic effect than IGF-1. Researchers also noted that “LR3 IGF-I remained more potent than IGF-I in several of these effects even when the peptides were given.[1]

The reduced affinity to IGF-1 binding proteins may also result in a shorter half-life of IGF-1 LR3 peptide. Animal suggest show that IGF-1 LR3 is eliminated within 4 hours.[2] At the same time, it may induce higher weight gain and organ mass increase in the tested animals compared to IGF-1.

The metabolites of IGF-1 LR3 may have a longer half-life and might remain detectable in test animals for up to 16 hours. In comparison, a high percentage of the natural IGF-1 appears to bind to IGF-1 binding proteins, which may reduce its effectiveness and prolongs half-life by up to 15 hours.[3]

According to one study in a mice model of muscular dystrophy, IGF-1 LR3peptide exposure appeared highly effective in reducing contraction-mediated injury.[4] Contraction damage is a major contributing factor to the pathophysiology of muscular dystrophy.

Another animal trial by Hill et al. also suggested that an IGF-1 LR3 exposure for 8 hours may have a protective effect against loss of muscle mass loss and muscle catabolism during periods of restricted energy intake and caloric deficit. The researchers reported that “Long(R3)-IGF-1 [exposure] tended to preserve whole-body and muscle protein in beef heifers on a low-quality diet.” The continuous exposure also led to significant suppression of the natural IGF-1 synthesis.[5]

One trial in guinea pigs also reported a significant increase in the organ weight of the animals after a 7-day exposure of IGF-1 LR3. The researchers note that the exposure most significantly enlarged the adrenals, gut, kidneys, and spleen.[6] It is important to note that IGF-1 LR3 and all other IGF-1 analogs are only hypothesized to mediate the anabolic effects of growth hormone.

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References


  1. Tomas FM, Lemmey AB, Read LC, Ballard FJ. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. J Endocrinol. 1996 Jul;150(1):77-84. DOI: 10.1677/joe.0.1500077. PMID: 8708565.
  2. Mongongu C, Coudoré F, Domergue V, Ericsson M, Buisson C, Marchand A. Detection of LongR3 -IGF-I, Des(1-3)-IGF-I, and R3 -IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes. Drug Test Anal. 2021 Jul;13(7):1256-1269. DOI: 10.1002/dta.3016. Epub 2021 Feb 22. PMID: 33587816.
  3. Guler HP, Zapf J, Schmid C, Froesch ER. Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. Acta Endocrinol (Copenh). 1989 Dec;121(6):753-8. doi: 10.1530/acta.0.1210753. PMID: 2558477.
  4. Gehrig SM, Ryall JG, Schertzer JD, Lynch GS. Insulin-like growth factor-I analogue protects muscles of dystrophic MDX mice from contraction-mediated damage. Exp Physiol. 2008 Nov;93(11):1190-8. Doi: 10.1113/expphysiol.2008.042838. Epub 2008 Jun 20. PMID: 18567600.
  5. Hill RA, Hunter RA, Lindsay DB, Owens PC. Action of long(R3)-insulin-like growth factor-1 on protein metabolism in beef heifers. Domest Anim Endocrinol. 1999 May;16(4):219-29. doi: 10.1016/s0739-7240(99)00015-6. PMID: 10370861.
  6. Conlon MA, Tomas FM, Owens PC, Wallace JC, Howarth GS, Ballard FJ. Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig. J Endocrinol. 1995 Aug;146(2):247-53. DOI: 10.1677/joe.0.1460247. PMID: 7561636.
  7. Kovacs GT, Worgall S, Schwalbach P, Steichele T, Mehls O, Rosivall L. Hypoglycemic effects of insulin-like growth factor-1 in experimental uremia: can concomitant growth hormone administration prevent this effect? Horm Res. 1999;51(4):193-200. doi: 10.1159/000023357. PMID: 10474022.
  8. MacDonald RS. The role of insulin-like growth factors in small intestinal cell growth and development. Horm Metab Res. 1999 Feb-Mar;31(2-3):103-13. DOI: 10.1055/s-2007-978706. PMID: 10226789.
  9. Dunaiski V, Dunshea FR, Walton PE, Goddard C. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs. J Endocrinol. 1997 Dec;155(3):559-65. DOI: 10.1677/joe.0.1550559. PMID: 9488001.
  10. Martha S, Pantam N, Thungathurthi S, Rao VL, Devarakonda K. Study of insulin resistance in relation to serum IGF-I levels in subjects with different degrees of glucose tolerance. Int J Diabetes Dev Ctries. 2008 Apr;28(2):54-9. DOI: 10.4103/0973-3930.43100. PMID: 19902049; PMCID: PMC2772007.
Adipotide (FTPP) and Fat Cells

Adipotide (FTPP) and Fat Cells

Adipotide peptide is a synthetic peptidomimetic and an experimental proapoptotic compound known as FTPP (Fat-Targeted Proapoptotic Peptide). Peptidomimetics are synthetic molecules that may mimic a natural protein’s structural domain. Adipotide appears to bind to the protein receptor prohibitin, which is why it also bears the name Prohibitin-targeting peptide 1 (Prohibitin-TP01). By doing so, it has proapoptotic potential on adipose tissue, meaning that it may induce cell death in white fat cells. Animal studies suggest that by inducing targeted apoptosis, Adipotide peptide may induce fat loss and improvement in several metabolic parameters.
 

Adipotide Peptide Overview

Adipotide FTPP appears to act by binding to the receptors for 2 specific proteins, ANXA2 (annexin A2) and prohibitin. Either of these receptors is expressed in various cells, but immunohistochemical analysis suggests that they form specific ANXA2-prohibitin receptor systems in white fat tissue.[1]

Research suggests that these receptors may play a role in regulating fatty acid transport in white adipose tissues.[2] Inhibiting the ANXA2 protein may lead to hypertrophy of white adipose cells due to reduced uptake of fatty acids.

On the other hand, prohibitin is a multifunctional membrane-associated protein that is thought to regulate cell survival and growth. It may trigger apoptosis by shuttling from the cell’s membrane to its nucleus.

Adipotide peptide has a unique structure consisting of the amino-acid sequence GKGGRAKDC-GG-D(KLAKLAK)2. The 9 amino acid sequence CKGGRAKDC appears to bear a specific affinity to the ANXA2-prohibitin receptor system found in the blood vessels supporting white adipose cells.[3] At the same time, (KLAKLAK)2 may disrupt mitochondrial membranes upon receptor-mediated cell internalization and induce programmed cell death.

As Adipotide peptide appears to bind to prohibitin in white adipose vasculature, it may trigger apoptosis and can result in the ablation of white fat cells.

According to research, Adipotide peptide and other similar peptidomimetics may potentially reduce subcutaneous and visceral fat and even target intra-organ fat, such as in fatty liver diseases.[4]

 

Research on Adipotide Peptide

Adipotide peptide may hold potential for two major research focuses –  obesity and cancer. Regarding its metabolic potential and the potential to induce fat loss, the peptidomimetic has been tested in mice, rats, and rhesus monkeys. In obese rats, 28 days of Adipotide peptide exposure led to a 30% reduction in body weight.[5] It also appeared to significantly suppress their appetite, even though the leptin levels of the animals plummeted. Furthermore, the energy expenditure of the animals was not apparently affected.

In another study, the researchers suggested that Adipotide peptide may have led to metabolic improvements as soon as the 3rd day of the study, even before there was a noticeable reduction in the body weight of the tested mice. Kim et al. concluded that Adipotide “rapidly and potently improved the glucose tolerance of obese mice in a weight- and food intake-independent manner.”[6] The peptidomimetic appeared to have reduced triglyceride and insulin levels as well.

In obese rhesus monkeys, Adipotide peptide exposure may have caused white adipose tissue blood vessels to undergo targeted apoptosis.[7] As a result, the tested animals lost weight and improved their insulin sensitivity within the first month of study. A significant decrease in white adipose tissue was noted by dual-energy x-ray absorptiometry and magnetic resonance imaging.

 

Adipotide Peptide and Prostate Cancer

The destruction of white fat may also have positive consequences for prostate cancer. This is suggested to be so, due to a high level of white fat that has been implicated as a critical contributing factor in poor prostate cancer outcomes.[8]

Studied have attempted to examine the impact of Adipotide peptide exposure in research models of prostate cancer. The study evaluated the action of a single cycle of Adipotide peptide in research models of castrate-resistant prostate cancer. According to the study, the models were put through the entire study cycle, but the study was terminated before completion.[9, 10]

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References


  1. Staquicini FI, Cardó-Vila M, Kolonin MG, Trepel M, Edwards JK, Nunes DN, Sergeeva A, Efstathiou E, Sun J, Almeida NF, Tu SM, Botz GH, Wallace MJ, O’Connell DJ, Krajewski S, Gershenwald JE, Molldrem JJ, Flamm AL, Koivunen E, Pentz RD, Dias-Neto E, Setubal JC, Cahill DJ, Troncoso P, Do KA, Logothetis CJ, Sidman RL, Pasqualini R, Arap W. Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18637-42. doi: 10.1073/pnas.1114503108. Epub 2011 Nov 2. PMID: 22049339; PMCID: PMC3219136.
  2. Salameh A, Daquinag AC, Staquicini DI, An Z, Hajjar KA, Pasqualini R, Arap W, Kolonin MG. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue. JCI Insight. 2016 Jul 7;1(10):e86351. doi: 10.1172/jci.insight.86351. PMID: 27468426; PMCID: PMC4959783.
  3. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004 Jun;10(6):625-32. doi: 10.1038/nm1048. Epub 2004 May 9. PMID: 15133506.
  4. Hossen N, Kajimoto K, Akita H, Hyodo M, Harashima H. A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication. J Control Release. 2013 Oct 28;171(2):104-12. doi: 10.1016/j.jconrel.2013.07.013. Epub 2013 Jul 18. PMID: 23871959.
  5. Kim DH, Woods SC, Seeley RJ. Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight. Diabetes. 2010 Apr;59(4):907-15. doi: 10.2337/db09-1141. Epub 2010 Jan 26. PMID: 20103704; PMCID: PMC2844838.
  6. Kim DH, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, Newgard CB, Woods SC, Seeley RJ. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes. 2012 Sep;61(9):2299-310. doi: 10.2337/db11-1579. Epub 2012 Jun 25. PMID: 22733798; PMCID: PMC3425411.
  7. Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, Pasqualini R. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011 Nov 9;3(108):108ra112. doi: 10.1126/scitranslmed.3002621. PMID: 22072637; PMCID: PMC3666164.
  8. Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013 May;63(5):800-9. doi: 10.1016/j.eururo.2012.11.013. Epub 2012 Nov 15. PMID: 23219374; PMCID: PMC3597763.
  9. Smith, T. L., Sidman, R. L., Arap, W., & Pasqualini, R. (2022). Targeting vascular zip codes: from combinatorial selection to drug prototypes. In The Vasculome (pp. 393-401). Academic Press.
  10. ClinicalTrials.gov [Internet]. National Library of Medicine (US). 2010 Dec 17 – . Identifier NCT01262664, A First-in-Man, Phase I Evaluation of A Single Cycle of Prohibitin Targeting Peptide 1 in Patients With Metastatic Prostate Cancer and Obesity; 2019 Jan 4; http://clinicaltrials.gov/ct2/show/NCT01262664
Semaglutide Research in Hormone Signaling

Semaglutide Research in Hormone Signaling

Semaglutide is a peptide agonist to the glucagon-like peptide-1 (GLP-1) receptors in the pancreas, the brain, and other organs. The hypothetical action of the compound is considered to be similar to GLP-1, a peptide hormone naturally produced in the intestine. It is an incretin, meaning it is considered to stimulate insulin secretion. Semaglutide is also a subject of extensive research, including pancreatic beta cell apoptosis and neuroprotective potential.

Semaglutide and Blood Sugar Control

Semaglutide has been hypothesized to act by activating the GLP-1 receptors in the pancreatic beta cells, stimulating insulin synthesis and release.[1][2] The stimulating effect on insulin synthesis is the primary mechanism via which Semaglutide may possibly lower both fasting and postprandial glucose levels. A meta-analysis of 26 RCTs suggests that Semaglutide may lower the fasting blood sugar levels and markers for long-term glucose control, such as HbA1c, in cases of type 2 diabetes.[3]

In addition to stimulating insulin secretion, Semaglutide may potentially reduce glucagon release and suppress hepatic gluconeogenesis.[4] These potential actions are supported by study findings in non-diabetic models, which lasted up to 12 weeks and reported over 38% reduction in blood sugar levels compared to a placebo after a carbohydrate-rich food delivery.[5] The researchers also suggested that Semaglutide may have slowed the speed of gastric emptying during the first hour after caloric intake compared to a placebo. The scientists suggested that this potential of Semaglutide may contribute to a gradual release of glucose and better glycemic control. Yet, the overall speed of gastric emptying over the entire 5-hour monitoring period after the meal appeared not affected.

Semaglutide has been hypothesized to reduce hyperglycemia without causing hypoglycemia. The risk of hypoglycemia is not considered to be higher when compared to a placebo as Semaglutide may possibly stimulate insulin secretion in a glucose-dependent manner.[6] In addition, the inhibition of glucagon release may not occur under hypoglycemic conditions.

 

Semaglutide and Weight

Semaglutide has been suggested to stimulate insulin secretion without leading to weight gain. Studies suggest that Semaglutide may reduce ad libitum energy intake, which may result in weight loss in the long term.[8] According to one study, Semaglutide reduced hunger hormone signaling to the brain, resulting in a reported 24% reduction in energy intake. Semaglutide may activate the GLP-1 receptors in the brain, which may play a major role in modulating appetite and reward-related behavior.[9] Furthermore, the potential of Semaglutide to slow down gastric emptying within the first hour of having a meal may also contribute to a reduced ad libitum energy intake.

 

Pancreatic Beta Cell Survival

Preliminary studies conducted in test animals suggest that Semaglutide may stimulate pancreatic beta cells’ survival and proliferation. These potential actions are considered to be of significant interest since cases of type 2 diabetes are often associated with pancreatic beta cell dysfunction and apoptosis in the long term.[10]

Animal research suggests that Semaglutide may help reverse the harmful changes of obesity and insulin resistance on pancreatic beta cells and stimulate their proliferation.[11] Researchers reveal that some studies also report that GLP-1 antagonists, such as Semaglutide, may protect pancreatic beta cells from apoptosis.[12] Several possible mechanisms are suggested in the protective potential of Semaglutide, and one of the most prominent is reducing the overload on the endoplasmic reticulum of the beta cells in diabetic conditions. GLP-1 receptor activation may also help stimulate autophagy, which prevents beta cell injury and death by protecting against inflammation and oxidative stress.

 

Semaglutide and Neuroprotection

Interestingly, Parkinson’s disease and type 2 diabetes are considered to share several genetic susceptibilities, such as single nucleotide polymorphisms in the growth factor signaling kinase gene Akt.[13] This has sparked interest in researching the potential of diabetes compounds for research studies on Parkinson’s disease. Currently, other GLP-1 receptor agonists, such as Exendin-4, have already been suggested to exhibit protective effects on Parkinson’s cases.[14] Another GLP-1 antagonist, Liraglutide, is under investigation for this hypothetical action.[16]

The research regarding the potential neuroprotective action of Semaglutide is still in its infancy, but many laboratory studies in animal models of PD suggest promising results.[15] The experiments report that Semaglutide may have neuroprotective characteristics and may increasethe survival of the dopaminergic neurons, the apoptosis of which is associated with the development of Parkinson’s.

In animals, Semaglutide appeared to have alleviated the chronic inflammatory responses in the brain, reduced lipid peroxidation, and increased the expression of growth factors that protect dopaminergic neurons in the substantia nigra and striatum.

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References:


  1. Dhillon S. Semaglutide: First Global Approval. Drugs. 2018 Feb;78(2):275-284. DOI: 10.1007/s40265-018-0871-0. PMID: 29363040.
  2. Hou Y, Ernst SA, Heidenreich K, Williams JA. Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP. Am J Physiol Gastrointest Liver Physiol. 2016 Jan 1;310(1):G26-33. doi: 10.1152/ajpgi.00293.2015. Epub 2015 Nov 5. PMID: 26542397; PMCID: PMC4698438.
  3. Zaazouee MS, Hamdallah A, Helmy SK, Hasabo EA, Sayed AK, Gbreel MI, Elmegeed AA, Aladwan H, Elshanbary AA, Abdel-Aziz W, Elshahawy IM, Rabie S, Elkady S, Ali AS, Ragab KM, Nourelden AZ. Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes. Diabetes Metab Syndr. 2022 Jun;16(6):102511. DOI: 10.1016/j.dsx.2022.102511. Epub 2022 May 20. PMID: 35623229.
  4. Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord. 2022 Jun;23(3):521-539. DOI: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID: 34993760; PMCID: PMC8736331.
  5. Hjerpsted JB, Flint A, Brooks A, Axelsen MB, Kvist T, Blundell J. Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity. Diabetes Obes Metab. 2018 Mar;20(3):610-619. DOI: 10.1111/dom.13120. Epub 2017 Oct 27. PMID: 28941314; PMCID: PMC5836914.
  6. Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021 Jul 7;12:645563. doi: 10.3389/fendo.2021.645563. Erratum in: Front Endocrinol (Lausanne). 2021 Nov 10;12:786732. PMID: 34305810; PMCID: PMC8294388.
  7. Mares AC, Chatterjee S, Mukherjee D. Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Curr Opin Cardiol. 2022 Jul 1;37(4):350-355. DOI: 10.1097/HCO.0000000000000955. Epub 2022 Feb 16. PMID: 35175229.
  8. Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, Hjerpsted JB. Effects of once-weekly Semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017 Sep;19(9):1242-1251. DOI: 10.1111/dom.12932. Epub 2017 May 5. PMID: 28266779; PMCID: PMC5573908.
  9. van Bloemendaal L, IJzerman RG, Ten Kulve JS, Barkhof F, Konrad RJ, Drent ML, Veltman DJ, Diamant M. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes. 2014 Dec;63(12):4186-96. DOI: 10.2337/db14-0849. Epub 2014 Jul 28. PMID: 25071023.
  10. Tomita T. Apoptosis in pancreatic β-islet cells in Type 2 diabetes. Bosn J Basic Med Sci. 2016 Aug 2;16(3):162-79. DOI: 10.17305/bjbms.2016.919. Epub 2016 May 22. PMID: 27209071; PMCID: PMC4978108.
  11. Marinho TS, Martins FF, Cardoso LEM, Aguila MB, Mandarim-de-Lacerda CA. Pancreatic islet cells disarray, apoptosis, and proliferation in obese mice. The role of Semaglutide treatment. Biochimie. 2022 Feb;193:126-136. doi: 10.1016/j.biochi.2021.10.017. Epub 2021 Nov 4. PMID: 34742857.
  12. Costes S, Bertrand G, Ravier MA. Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies. Int J Mol Sci. 2021 May 18;22(10):5303. doi: 10.3390/ijms22105303. PMID: 34069914; PMCID: PMC8157542.
  13. Xiromerisiou G, Hadjigeorgiou GM, Papadimitriou A, Katsarogiannis E, Gourbali V, Singleton AB. Association between AKT1 gene and Parkinson’s disease: a protective haplotype. Neurosci Lett. 2008 May 9;436(2):232-4. doi: 10.1016/j.neulet.2008.03.026. Epub 2008 Mar 15. PMID: 18395980; PMCID: PMC8958471.
  14. Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K, Hibbert S, Budnik N, Zampedri L, Dickson J, Li Y, Aviles-Olmos I, Warner TT, Limousin P, Lees AJ, Greig NH, Tebbs S, Foltynie T. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Oct 7;390(10103):1664-1675. DOI: 10.1016/S0140-6736(17)31585-4. Epub 2017 Aug 3. PMID: 28781108; PMCID: PMC5831666.
  15. Zhang L, Zhang L, Li L, Hölscher C. Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson’s Disease. J Parkinsons Dis. 2019;9(1):157-171. DOI: 10.3233/JPD-181503. PMID: 30741689.
  16. Clinical trial identifier NCT02953665
Research in Wrinkle Reduction and Vialox

Research in Wrinkle Reduction and Vialox

Vialox peptide (also known as Pentapeptide-3V) has been suggested to exhibit potential in preventing muscle contraction by exhibiting a curare-like effect at the neuromuscular junction, disallowing the nervous system signals from reaching the muscles. Vialox peptide is of interest because of its potential to communicate between muscles and nerves.

Vialox peptide has been suggested to interfere with nerve and muscle signal transmission. Signals are transmitted in normal conditions after nerves release acetylcholine from their axons. Contraction may occur after acetylcholine transportation through the neuromuscular junction and binds to a receptor on the muscle.

Vialox peptide may halt contraction by binding to the AChR.[2] Acetylcholine is prevented from binding due to this action, which may induce less binding and fewer muscle contractions.

At the neuromuscular junction, sodium ion release is constrained due to acetylcholine binding to a muscle receptor. Depolarization occurs, which may cause electrical pulses to develop wrinkling and creasing via the muscle contraction. Vialox may inhibit this process by binding to AChR. Vialox peptide inhibits acetylcholine binding when it binds to AChR.

Vialox peptide has been suggested to only affect peripheral AChRs and may not affect central neuronal receptors. Unlike the other nicotinic acetylcholine receptor antagonists. This process suggests that Vialox only acts on the neuromuscular junction. Vialox peptide may potentially reduce skin texture in research cases by up to 11% and relief by 8%, according to one study. Since wrinkle size and ease are considered to be inversely proportional, Vialox may potentially reduce wrinkle development by an average of 8%. Approximately 60% and 47% of the animal subjects were studied.

Vialox (Pentapeptide-3V), composed of lysine, threonine, and serine, is considered to stimulate collagen production while tightening the skin by acting directly on the dermis. Vialox may potentially boost melanin production, a considered protectant against UV damage.

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References


  1. Zhmak, M. N., Utkin, Y. N., Andreeva, T. V., Kudryavtsev, D. S., Kryukova, E. V., Tsetlin, V. I., … & Shelukhina, I. V. E. (2017). U.S. Patent No. 9,550,808. Washington, DC: U.S. Patent and Trademark Office.
  2. Reddy, B. Y., Jow, T., & Hantash, B. M. (2012). Bioactive oligopeptides in dermatology: Part II. Experimental dermatology, 21(8), 569-575. https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2012.01527.x