Summary
To study whether abnormal secretion of islet amyloid polypeptide is involved in the development of insulin resistance and impaired insulin secretion in Type 2 (noninsulin-dependent) diabetes mellitus, we measured islet amyloid polypeptide concentrations in 56 first-degree relatives of Type 2 diabetic subjects and in 10 healthy control subjects. Fasting islet amyloid polypeptide concentrations were similar in control subjects, glucose-tolerant and glucose-intolerant relatives (8±1, 9±1 and 11±2 fmol/ml; p=NS). The area under the islet amyloid polypeptide curve measured during an oral glucose load was larger in glucose-intolerant relatives (115±13 fmol/ml) compared to glucose tolerant relatives and control subjects (88±3 and 79±12 fmol/ml; p<0.05). The insulin response during the oral glucose load was inversely correlated with the rate of glucose disposal measured during a euglycaemic hyperinsulinaemic clamp (r=−0.725; p<0.01), while no significant correlation was observed between the corresponding values for islet amyloid polypeptide and glucose disposal (r=−0.380; p=NS). Hypersecretion of islet amyloid polypeptide is observed in glucose-intolerant first-degree relatives of patients with Type 2 diabetes. Since these patients are characterized by insulin resistance and abnormal first-phase insulin secretion, the putative role of islet amyloid polypeptide in the development of these abnormalities remains to be established. It is however, unlikely that islet amyloid polypeptide is involved in the development of insulin resistance as insulin-resistant relatives with normal glucose-tolerance showed normal islet amyloid polypeptide concentrations.
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Eriksson J, Franssila-Kallunki A, Ekstrand A et al. (1989) Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med 321: 337–343
Leighton B, Cooper GJS (1988) Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature 335: 632–635
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 Bio-phys Res Commun 160: 961–967
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
Frontoni S, Choi SB, Banduch D, Rosetti L (1991) In vivo insulin resistance induced by amylin primarily through inhibition of insulin-stimulated glycogen synthesis in skeletal muscle. Diabetes 40: 568–573
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
Asai J, Nakazato M, Miyazato M, Kangawa K, Matsuo H, Matsukura S (1990) Regional distribution and molecular forms of rat islet amyloid polypeptide. Biochem Biophys Res Commun 169: 788–795
Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR (1990) Slow glucose removal rate of hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 113: 909–915
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
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
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Eriksson, J., Nakazato, M., Miyazato, M. et al. Islet amyloid polypeptide plasma concentrations in individuals at increased risk of developing Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 35, 291–293 (1992). https://doi.org/10.1007/BF00400933
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DOI: https://doi.org/10.1007/BF00400933