Summary
The response of islet amyloid polypeptide and insulin and their molar ratios were investigated in eight healthy volunteers before and after treatment with dexamethasone by oral and frequently-sampled intravenous glucose tolerance tests. Following dexamethasone treatment the insulin sensitivity index decreased significantly from 6.5±1.3 to 4.1±1.0 (μU·ml−1·min−1, p<0.05. The area under the curve representing above-basal levels of insulin during oral glucose tolerance test increased significantly following dexamethasone treatment from 48132±9736 to 82230±14846 pmol·l−1·3 h−1, p<0.05, the area under the curve of islet amyloid polypeptide increased from 1308±183 to 2448±501 pmol·l−1·3h−1, p<0.05. The overall insulin/islet amyloid polypeptide molar ratios calculated from the area under the curve during the 3-h period of the oral glucose tolerance test was not significantly different before and after dexamethasone treatment (42±5 vs 40±4). During the oral glucose tolerance test the insulin/islet amyloid polypeptide ratio increased significantly from baseline to 30 min (p<0.05), then declined towards initial values before and after dexamethasone treatment. In conclusion, dexamethasone induced a significant decrease in insulin sensivity and a significant increase in insulin secretion during the oral glucose tolerance test. However, in contrast to previous animal experiments we did not find a change in the insulin/islet amyloid polypeptide ratio before and after dexamethasone treatment.
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Opie EL (1900) On the relation of chronic interstitial pancreatitis to the islands of Langerhans and to diabetes mellitus. J Exp Med 5: 397–428
Ehrlich JC, Ratner JM (1961) Amyloidosis of the islets of Langerhans: a restudy of islet hyalin in diabetic and nondiabetic individuals. Am J Pathol 38: 49–59
Westermark P, Wilander E, Westermark GT, Johnson KH (1987) Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals. Diabetologia 30: 887–892
Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH (1987) Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic rat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci USA 84: 3881–3885
Cooper GJS, Willis A, Clark A, Turner RC, Sim RB, Reid KBM (1987) Purification and characterization of amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci USA 84: 8628–8632
Lukinius A, Wilander E, Westermark GT, Engström U, Westermark P (1989) Co-localization of islet amyloid polypeptide and insulin in the B cell secretory granules of the human pancreatic islets. Diabetologia 32: 240–244
Kahn S, D'Alessio DA, Schwartz MW et al. (1990) Evidence of cosecretion of islet amyloid polypeptide and insulin by B cells. Diabetes 39: 634–638
Hartter E, Svoboda T, Ludvik B et al. (1991) Basal and stimulated plasma levels of pancreatic amylin indicate its co-secretion with insulin in humans. Diabetologia 34: 52–54
Mitsukawa T, Takemura J, Asai J et al. (1990) Islet amyloid polypeptide response to glucose, insulin and somatostatin analogue administration. Diabetes 39: 639–642
Butler PC, Chou J, Carter WB et al. (1990) Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans. Diabetes 39: 752–756
Ludvik B, Lell B, Hartter E, Schnack C, Prager R (1991) Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes. Diabetes 40: 1615–1619
Sanke T, Hanabusa T, Nakano Y et al. (1991) Plasma islet amyloid polypeptide (amylin) levels and their responses to oral glucose in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 34: 129–132
Ohsawa H, Kanatsuka A, Yamaguchi T, Makino H, Yoshida S (1989) Islet amyloid polypeptide inhibits glucose-stimulated insulin secretion from isolated rat pancreatic islets. Biochem Biophys Res Commun 160: 961–967
Leighton B, Garth JS, Cooper GJS (1988) Pancreatic amylin and calcitonin gene related peptide (CGRP) cause resistance to insulin in skeletal muscle in vitro. Nature 335: 632–635
Molina JM, Cooper GJS, Leighton B, Olefsky JM (1990) Induction of insulin resistance in vivo by amylin and calcitonin generelated peptide. Diabetes 39: 260–265
Sowa R, Sanke T, Hirayama J et al. (1990) Islet amyloid polypeptide amide causes peripheral insulin resistance in vivo in dogs. Diabetologia 33: 118–120
Nagamatsu S, Caroll RJ, Grodsky GM, Steiner DF (1990) Lack of islet amyloid polypeptide regulation of insulin biosynthesis or secretion in normal rat islets. Diabetes 39: 871–874
Bretherton-Watt D, Gilbey SG, Ghatei MA, Beacham J, Bloom SR (1990) Failure to establish islet amyloid polypeptide (amylin) as a circulating beta cell inhibiting hormone in man. Diabetologia 33: 115–117
Ludvik B, Berzlanovich A, Hartter E, Lell B, Prager R, Graf H (1990) Increased amylin levels in patients on chronic hemodialysis. Neph Dial Transpl 8: 694–695 (Abstract)
Inoue K, Hisatomi A, Umeda F, Nawata H (1991) Release of amylin from perfused rat pancreas in response to glucose arginine, β-hydroxybutyrate, and gliclazide. Diabetes 40: 1005–1009
Bretherton-Watt D, Ghatei MA, Bloom SR et al. (1989) Altered islet amyloid polypeptide (amylin) gene expression in rat models of diabetes. Diabetologia 32: 881–883
O'Brien TD, Westermark P, Johnson KH (1991) Islet amyloid polypeptide and insulin secretion from isolated perfused pancreas of fed, fasted, glucose-treated, and dexamethasone-treated rats. Diabetes 40: 1701–1706
Pacini G, Bergman RN (1986) MINMOD: computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Comp Meth Progr Biomed 23: 113–122
Hartter E, Svoboda T, Lell B et al. (1990) Reduced islet amyloid polypeptide in insulin-dependent diabetes mellitus. Lancet I:854 (Letter)
Johnson KH, O'Brien TD, Jordan K, Westermark P (1989) Impaired glucose tolerance is associated with increased islet amyloid polypeptide (IAPP) immunoreactivity in pancreatic beta cells. Am J Pathol 135: 245–250
Eriksson J, Nakazato M, Miyazato M, Shiomi K, Matsukura S, Groop L (1992) Islet amyloid polypeptide plasma concentrations in individuals at increased risk of developing type 2 (non-insulindependent) diabetes mellitus. Diabetologia 35: 291–293
Ogawa A, Harris V, McCorkle SK, Unger RH, Luskey KL (1990) Amylin secretion from the rat pancreas and its selective loss after streptozotocin. J Clin Invest 85: 973–976
Swenne I (1992) Pancreatic beta-cell growth and diabetes. Diabetologia 35: 193–201
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Ludvik, B., Clodi, M., Kautzky-Willer, A. et al. Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans. Diabetologia 36, 84–87 (1993). https://doi.org/10.1007/BF00399099
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DOI: https://doi.org/10.1007/BF00399099