This trial shows the effectiveness of BPC157 on damages caused by insulin over dosage, which can be very useful for diabetics who inject themselves too much insulin… extracts:
OVER-DOSE INSULIN AND STABLE GASTRIC PENTADECAPEPTIDE BPC 157. ATTENUATED GASTRIC ULCERS, SEIZURES, BRAIN LESIONS, HEPATOMEGALY, FATTY LIVER, BREAKDOWN OF LIVER GLYCOGEN, PROFOUND HYPOGLYCEMIA AND CALCIFICATION IN RATS
The general significance of insulin induced ulcers remains not determined. We focused on hyperinsulinemia, deliberate injection of excessive insulin, and possibility that an anti-ulcer therapy with anti-ulcer peptide may be more successful counteracting therapy.
Insulin induced ulcers were long ago described, and related to gastric acid hypersecretion (1, 2).
Thus, to provide some novel intriguing insights, we focused on insulin induced gastric ulcers (1, 2) and then on other disturbances that may be concomitantly induced by insulin application (3-5).
We focused on a peptide therapy, using a small, orally active, anti-ulcer peptide (7-11) stable gastric pentadecapeptide BPC 157 (MW 1419) with very safe profile (LD1 could be not achieved, no side effects in clinical trials (12, 13) stable in human gastric juice (14), effective in trials for inflammatory bowel disease therapy (12, 13) and wound healing (15-18) also in diabetic rats (18, 19).
Importantly, pentadecapeptide BPC 157 was more active than recombinant human platelet-derived growth factor (PDGF-BB), stimulating both expression of early growth response 1 (egr-1) gene and its repressor nerve growth factor 1- A binding protein-2 (NAB2) (18).
Thereby, it may be important for cytokine induction, growth factor generation, early extracellular matrix (collagen) formation (18), but also for gluconeogenesis regulation (20).
Finally, alloxan-gastric ulcers in rats and mice may be inhibited by stable gastric pentadecapeptide BPC 157 (21).
Thus, when given to insulin-rats, BPC 157 would be confronted with the all processes simultaneously occurring that eventually lead to stomach ulcer (1, 2), hypoglycemia and all mentioned disturbances and death in insulin over-dose-rats (3-5). However, we shown that pentadecapeptide BPC 157, as an antiulcer peptide (7-11), may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. This may also indicate that these disturbances are also interconnected throughout BPC 157 background. Moreover, considering the used insulin (250 IU/kg i.p.) /BPC 157 (10 µg, 10 ng/kg i.p. or i.g.) ratio (7, 8), it may be reasonably to assume that these therapy effects may indicate a likely role of BPC 157 in insulin controlling and influence on one or more causative process(es).
In conclusion, these findings demonstrate that when one application of very high dose of insulin may induce together stomach ulcer, seizures, severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, breakdown of liver glycogen with profound hypoglycemia, along with calcium deposition, and finally fatal outcome in rats, all damages were markedly attenuated when BPC 157 was applied.
The same effectiveness when given intraperitoneally or intragastrically (i.e., stable in human gastric juice (14)) may be suggestive that BPC 157 may have also an incretin role in controlling insulin effects (7, 8, 11).
Intriguingly, further studies may show whether standard anti-ulcer agents that prevent insulin-stomach ulcer (1, 2) may also have a broader beneficial effect on other disturbances presented in insulin-rats.
Previously, BPC 157 was shown to counteract toxic effects of other insulin preparations (43).
- 7. Sikiric P, Petek M, Rucman R, et al. A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC. J Physiol (Paris) 1993; 87: 313-327.
- 8. Sikiric P, Seiwerth S, Brcic L, et al. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response. Inflammopharmacology 2006; 14: 214-221.
- 9. Sikiric P, Siwerth S, Grabarevic Z, et al. The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesion induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promoters and gut peptides. Life Sci 1994; 54: 63-68.
- 10. Sikiric P, Seiwerth, S, Grabarevic Z, et al. The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure. Eur J Pharmacol 1997; 332: 23-33.
- 11. Sikiric P, Seiwerth S, Grabarevic Z, et al. Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats. Dig Dis Sci 1996; 41: 1518-1526.
- 12. Veljaca M, Pavic-Sladoljev D, Mildner B, et al. Safety, tolerability and pharmacokinetics of PL 14736, a novel agent for treatment of ulcerative colitis, in healthy male volunteers. Gut 2003; 51: A309.
- 13. Ruenzi M, Stolte M, Veljaca M, Oreskovic K, Peterson J. A multicenter, randomized, double blind, placebo-controlled phase II study of PL 14736 enema in the treatment of mild-to-moderate ulcerative colitis. Gastroenterology 2005; 128: A584.
- 14. Veljaca M, Chan K, Guglietta A. Digestion of h-EGF, h-TGF alpha and BPC 157 in human gastric juice. Gastroenterology 1995; 108: 761.
- 15. Sikiric P, Seiwerth S, Mise S, et al. Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice. Burns 2003; 29: 323-334.
- 16. Novinscak T, Brcic L, Staresinic M, et al. Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat. Surg Today 2008; 38: 716-725.
- 17. Staresinic M, Petrovic I, Novinscak T, et al. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. J Orthop Res 2006; 24: 1109-1117.
- 18. Tkalcevic VI, Cuzic S, Brajsa K, et al. Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression. Eur J Pharmacol 2007; 570(1-3): 212-221.
- 20. Berasi SP, Huard C, Li D, et al. Inhibition of gluconeogenesis through transcriptional activation of EGR1 and DUSP4 by AMP-activated kinase. J Biol Chem 2006; 281: 27167-27177.
- 21. Petek M, Sikiric P, Anic T, et al. Pentadecapeptide BPC 157 attenuates gatric lesions induced by alloxan in rats and mice. J Physiol (Paris) 1999; 93: 501-504.
- 43. Ilic S, Mester M, Filipovic M, et al. Stable gastric pentadecapeptide BPC 157 and insulin induced gastric lesions in rats. J Physiol Pharmacol 2009; 60(Suppl 2): 40.