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Amylin dual action: a second gluco regulatory β-cell hormone, treatment and cause for the diabetes

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Abstract

Amylin also known as islets of amyloid polypeptides (IAPP), is a secretary product of pancreatic β -cells, co-synthesized and co-secreted with insulin. It is a glucose regulatory β -cell hormone with a central action on food intake; it inhibits glucagon secretion, delays gastric emptying and acts as a satiety agent. It has been proposed to have a role in the management of diabetes. Pramlintide a synthetic version of amylin is used in glycemic control of diabetes mellitus. Accumulation of amyloid on β- cell often reflects the severity of diabetes. This review is primarily focused on dual role of amylin: induction as well as treatment of Diabetes.

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References

  1. Gavin JR, Alberti KG, Davidson MB, DeFronzo RA, Drash A, Gabbe SG, et al. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20:1183–97.

    Google Scholar 

  2. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. β-Cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003;52:102–10.

    Article  PubMed  CAS  Google Scholar 

  3. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type-2 diabetes. Diabetologia. 2003;46:3–19.

    Article  PubMed  CAS  Google Scholar 

  4. The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–98.

    Article  Google Scholar 

  5. The UKPDS Study Group. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995;44:1249–58.

    Article  Google Scholar 

  6. The DCCT/EDIC Research Group. Retinopathy and nephropathy in patients with type 1 diabetes 4 years after a trial of intensive therapy. N Engl J Med. 2000;342:381–9.

    Article  Google Scholar 

  7. Roberts AN, Leighton B, Todd JA. Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus. Proc Natl Acad Sci U S A. 1990;86:9662–6.

    Article  Google Scholar 

  8. Sexton PM, Paxinos G, Kenney MA, Wookey PJ, Beaumont K. In vitro autoradiographic localization of Amylin binding sites in rat brain. Neuroscience. 1994;62:553–67.

    Article  PubMed  CAS  Google Scholar 

  9. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 1998;393:333–9.

    Article  PubMed  CAS  Google Scholar 

  10. Chin SY, Hall JM, Brain SD, Morton IK. Vasodilator responses to calcitonin gene-related peptide (CGRP) and amylin in the rat isolated perfused kidney are mediated via CGRP1 receptors. J Pharmacol Exp Ther. 1994;269:989–92.

    PubMed  CAS  Google Scholar 

  11. Wookey PJ, Tikellis C, Du H-C, Qin H-F, Sexton PM, Cooper ME. Amylin binding on rat renal cortex, stimulation of adenylyl cyclase and activation of plasma renin. Am J Physiol. 1996;270:289–94.

    Google Scholar 

  12. Christopoulos G, Perry K, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, et al. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol. 1999;56:235–42.

    PubMed  CAS  Google Scholar 

  13. Mulder H, Ekelund M, Ekblad E, Sundler F. Islet amyloid polypeptide in the gut and pancreas: localization, ontogeny and gut motility effects. Peptides. 1997;18:771–83.

    Article  PubMed  CAS  Google Scholar 

  14. Ferrier G, Pierson A, Jones P, Bloom S, Girgis S, Legon S. Expression of rat amylin (IAPP/DAP) gene. J Mol Endocrinol. 1989;3:R1–4.

    Article  PubMed  CAS  Google Scholar 

  15. Guidobono F. Amylin and gastrointestinal activity. Gen Pharmacol. 1998;31:173–7.

    Article  PubMed  CAS  Google Scholar 

  16. Hoppener JW, Lips CJ. Role of islet amyloid in type 2 diabetes mellitus. Int J Biochem Cell Biol. 2006;38:726–36.

    Article  PubMed  Google Scholar 

  17. Zhang S, Liu H, Yu H, Garth JS. Cooper. Fas-Associated Death Receptor Signaling Evoked by Human Amylin in Islet β-Cells. Diabetes. 2008;57:348–56.

    Article  PubMed  CAS  Google Scholar 

  18. Kapurniotu A. Amyloidogenicity and cytotoxicity of islet amyloid polypeptide. Biopolymers. 2001;60:438–59.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang SP, Liu JX, Saafi EL, Cooper GJS. Induction of apoptosis by human amylin in RINm5F islet beta-cells is associated with enhanced expression of p53 and p21 (WAF1/CIP1). FEBS Lett. 1999;455:315–20.

    Article  PubMed  CAS  Google Scholar 

  20. Couce M, Kane LA, O’Brien TD, Charlesworth J, et al. Treatment with growth hormone and dexamethasone in mice transgenic for human islet amyloid polypeptide causes islet amyloidosis and β-cell dysfunction. Diabetes. 1996;45:1094–101.

    Article  PubMed  CAS  Google Scholar 

  21. Verchere CB, D’Alessio DA, Palmiter RD, Weir GC, Bonner-Weir S, Baskin DG, et al. Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide. Proc Natl Acad Sci U S A. 1996;93:3492–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC. The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediatesized toxic amyloid particles. Diabetes. 1999;48:491–8.

    Article  PubMed  CAS  Google Scholar 

  23. Janciauskiene S, Ahren B. Fibrillar islet amyloid polypeptide differentially affects oxidative mechanisms and lipoprotein uptake in correlation with cytotoxicity in two insulin-producing cell lines. Biochem Biophys Res Commun. 2000;267:619–25.

    Article  PubMed  CAS  Google Scholar 

  24. Lin CY, Gurlo T, Kayed R, Butler AE, Haataja L, Glabe CG, et al. Toxic human islet amyloid polypeptide (h-IAPP) oligomers are intracellular, and vaccination to induce anti-toxic oligomer antibodies does not prevent h-IAPP–induced β-cell apoptosis in h-IAPP transgenic mice. Diabetes. 2007;56:1324–32.

    Article  PubMed  CAS  Google Scholar 

  25. Oyadomari S, Koizumi A, Takeda K, Gotoh T, Akira S, Araki E, et al. Targeted disruption of the chop gene delays endoplasmic reticulum stress-mediated diabetes. J Clin Invest. 2002;109:525–32.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Zhang SP, Liu JX, MacGibbon G, Dragunow M, Cooper GJS. Increased expression and activation of c-Jun contributes to human amylin-induced apoptosis in pancreatic islet beta-cells. J Mol Biol. 2002;324:271–85.

    Article  PubMed  CAS  Google Scholar 

  27. Gomez-foix AM, Rodriguez-gilt JE, Guinovart JJ. Anti-insulin effects of amylin and calcitonin-gene-related peptide On hepatic glycogen metabolism. Biocher J. 1991;276:607–10.

    CAS  Google Scholar 

  28. Cooper GJS, Day AJ, Willis AC, Roberts AN, Reid KBM, Leighton B. Amylin and the amylin gene: structure, function and relationship to islet amyloid and to diabetes mellitus. Biochim Biophys Acta. 1989;1014:247–58.

    Article  PubMed  CAS  Google Scholar 

  29. Young AA, Gedulin BR, Rink TJ. Dose-responses for the slowing of gastric emptying in a rodent model by glucagon-like peptide (7–36) NH2, amylin, cholecystokinin, and other possible regulators of nutrient uptake. Metabolism. 1996;45:1–3.

    Article  PubMed  CAS  Google Scholar 

  30. Gedulin B, Jodka D, Green D, et al. Amylin inhibition of arginine induced glucagon secretion: comparison with glucagon like peptide- 1 (7–36)-amide (GLP-1). Diabetologia. 1996;39 Suppl 1:A154.

    Google Scholar 

  31. Bhavsar S, Watkins J, Rink T. Synergistic effect of amylin and cholecystokinine octapeptide on food intake in mice. Diabetes. 1996;45:333A.

    Google Scholar 

  32. Fineman MS, Giotta MP, Thompson RG, Kolterman OG, Koda JE. Amylin response following Sustacal ingestion is diminished in type II diabetic patients treated with insulin. Diabetologia. 1996;39 Suppl 1:A149.

    Google Scholar 

  33. Young AA. Amylin’s physiology and its role in diabetes. Curr Opin Endocrinol Diabetes. 1997;4:282–90.

    Article  CAS  Google Scholar 

  34. Kruger DF, Gloster MA. Pramlintide for the treatment of insulin requiring diabetes mellitus: rationale and review of clinical data. Drugs. 2004;64:1419–32.

    Article  PubMed  CAS  Google Scholar 

  35. Gedulin BR, Rink TJ, Young AA. Dose–response for glucagonostatic effect of amylin in rats. Metabolism. 1997;46:67–70.

    Article  PubMed  CAS  Google Scholar 

  36. Silvestre RA, Rodriguez-Gallardo J, Jodka C, Parkes DG, Pittner RA, Young AA, et al. Selective amylin inhibition of the glucagon response to arginine is extrinsic to the pancreas. Am J Physiol Endocrinol Metab. 2001;280:E443–9.

    PubMed  CAS  Google Scholar 

  37. Young AA, Gedulin B, Vine W, Percy A, Rink TJ. Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin. Diabetologia. 1995;38:642–8.

    Article  PubMed  CAS  Google Scholar 

  38. Lutz TA, Del Prete E, Scharrer E. Reduction of food intake in rats by intraperitoneal injection of low doses of amylin. Physiol Behav. 1994;55:891–5.

    Article  PubMed  CAS  Google Scholar 

  39. Beaumont K, Kenney MA, Young AA, Rink TJ. High affinity amylin binding sites in rat brain. Mol Pharmacol. 1993;44:493–7.

    PubMed  CAS  Google Scholar 

  40. Westermark P, Engstrom U, Johnson KH, Westermark GT, Betsholtz C. Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation. Proc Natl Acad Sci U S A. 1990;87:5036–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Colburn WA, Gottlieb AB, Koda J, Kolterman OG. Pharmacokinetics and pharmacodynamics of AC137 (25,28,29 tripro-amylin, human) after intravenous bolus and infusion doses in patients with insulin-dependent diabetes. J Clin Pharmacol. 1996;36:13–24.

    Article  PubMed  CAS  Google Scholar 

  42. Jones MC. Therapies for diabetes: pramlintide and exenatide. Am Fam Physician. 2007;75:1831–5.

    PubMed  Google Scholar 

  43. Schvarcz E, Palmer M, Aman J, Horowitz M, Stridsberg M, Berne C. Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin dependent diabetes mellitus. Gastroenterology. 1997;113:60–6.

    Article  PubMed  CAS  Google Scholar 

  44. Kong MF, King P, Macdonald IA, Stubbs TA, Perkins AC, Blackshaw PE, et al. Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM. Diabetologia. 1997;40:82–8.

    Article  PubMed  CAS  Google Scholar 

  45. Unger RH, Orci L. The role of glucagon in the endogenous hyperglycemia of diabetes mellitus. Ann Rev Med. 1977;28:119–30.

    Article  PubMed  CAS  Google Scholar 

  46. Unger RH, Aguilar-Parada E, Muller WA, Eisentraut AM. Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest. 1970;49:837–48.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  47. Edelman SV, Weyer C. Unresolved challenges with insulin therapy in type 1 and type 2 diabetes: potential benefit of replacing amylin, a second beta-cell hormone. Diabetes Technol Ther. 2002;4:175–89.

    Article  PubMed  CAS  Google Scholar 

  48. Alexander JK. Obesity and coronary heart disease. Am J Med Sci. 2001;321:215–24.

    Article  PubMed  CAS  Google Scholar 

  49. Vidal J. Updated review on the benefits of weight loss. Int J Obes Relat Metab Disord. 2002;26 Suppl 4:S25–8.

    Article  PubMed  Google Scholar 

  50. Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord. 1992;16:397–415.

    PubMed  CAS  Google Scholar 

  51. Williamson DF, Thompson TJ, Thun M, Flanders D, Pamuk E, Byers T. Intentional weight loss and mortality among overweight individuals with diabetes. Diabetes Care. 2000;23:1499–504.

    Article  PubMed  CAS  Google Scholar 

  52. Weyer C, Gottlieb A, Kim DD, Lutz K, Schwartz S, Gutierrez M, et al. Pramlintide reduces postprandial glucose excursions when added to regular insulin or insulin lispro in subjects with type 1 diabetes: a dose-timing study. Diabetes Care. 2003;26:3074–9.

    Article  PubMed  CAS  Google Scholar 

  53. Halford JC. Obesity drugs in clinical development. Curr Opin Investig Drugs. 2006;7:312–8.

    PubMed  CAS  Google Scholar 

  54. Ratner RE, Dickey R, Fineman M. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long term glycaemic and weight control in Type 1 diabetes mellitus: a 1 year randomized controlled trial. Diabet Med. 2004;21:1204–12.

    Article  PubMed  CAS  Google Scholar 

  55. Hollander P, Maggs DG, Ruggles JA, Fineman M, Shen L, Kolterman OG, et al. Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obes Res. 2004;12:661–8.

    Article  PubMed  CAS  Google Scholar 

  56. Edelman SV, Garg SK, Frias JP, Maggs D, Wang Y, Strobel SA, et al. A double-blind, placebo controlled trial asessing pramlintide teatment in the setting of intensive insulin therapy in type 1 diabetes. Diabetes Care. 2006;29:2189–95.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, P. Wadhwani College of Pharmacy, Yavatmal, 445001, MS, India

    Alok S. Tripathi, Paresh J. Wadhwani, Shirish Marathe & Pratik G. Mahajan

  2. Department of Chemistry, P. Wadhwani College of Pharmacy, Yavatmal, 445001, MS, India

    Anil V. Chandewar

  3. Birla Institute of Technology, Mesra, Ranchi, 835 215, Jharkhand, India

    Papiya M. Majumder

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  1. Alok S. Tripathi
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Correspondence to Alok S. Tripathi.

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Tripathi, A.S., Wadhwani, P.J., Majumder, P.M. et al. Amylin dual action: a second gluco regulatory β-cell hormone, treatment and cause for the diabetes. Int J Diabetes Dev Ctries 34, 125–129 (2014). https://doi.org/10.1007/s13410-014-0203-1

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