Lack of Acute Effect of Amylin (islet Associated Polypeptide) on Insulin Sensitivity During Hyperinsulinaemic Euglycaemic Clamp in Humans

Overview

Journal Diabetologia

Specialty Endocrinology

Date 1994 Feb 1

PMID 8163050

Citations 3

Authors

J P Wilding

W M Bennet

S G Gilbey

J Beacham

M A Ghatei

S R Bloom

Affiliations

Soon will be listed here.

Abstract

It is suggested that amylin (islet associated polypeptide), co-secreted with insulin from the pancreatic beta cells acts as a circulating hormone which opposes the action of insulin on muscle and increases hepatic glucose production. We have tested the effect of amylin in human subjects on postabsorptive glucose homeostasis and on insulin sensitivity using the euglycaemic hyperinsulinaemic clamp. The amylin used opposed insulin-mediated glucose disposal in rat soleus muscle at concentrations of 10 nmol/l. Seven subjects were studied on two occasions and infused with either amylin or placebo for 6 h, initially when postabsorptive and then during a euglycaemic hyperinsulinaemic clamp. Mean plasma amylin concentrations during the first 3 h were 2006 +/- 327 pmol/l during amylin infusion and 20 +/- 9 pmol/l during the control infusion. Amylin infusion had no effect on postabsorptive plasma concentrations of insulin (control: 32 +/- 16 vs amylin: 25 +/- 8 pmol/l) or glucose (5.1 +/- 0.1 vs 5.3 +/- 0.1 mmol/l). During the clamp, amylin concentrations were 1636 +/- 422 pmol/l when it was infused and 24 +/- 6 during control infusions. Plasma glucose and insulin concentrations were well matched during the control and amylin infusions (glucose: 4.7 +/- 0.1 vs 4.8 +/- 0.1 mmol/l; insulin: 198 +/- 37 vs 195 +/- 22 pmol/l). Exogenous glucose infusion rates were a mean of 13% lower than control values during the amylin infusion but were not statistically different (p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

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References

Frontoni S, Choi S, Banduch D, Rossetti L . In vivo insulin resistance induced by amylin primarily through inhibition of insulin-stimulated glycogen synthesis in skeletal muscle. Diabetes. 1991; 40(5):568-73. DOI: 10.2337/diab.40.5.568. View

Sowa R, Sanke T, Hirayama J, Tabata H, Furuta H, Nishimura S . Islet amyloid polypeptide amide causes peripheral insulin resistance in vivo in dogs. Diabetologia. 1990; 33(2):118-20. DOI: 10.1007/BF00401051. View

Koopmans S, van Mansfeld A, Jansz H, Krans H, Radder J, Frolich M . Amylin-induced in vivo insulin resistance in conscious rats: the liver is more sensitive to amylin than peripheral tissues. Diabetologia. 1991; 34(4):218-24. DOI: 10.1007/BF00405079. View

Shiomi K, Nakazato M, Miyazato M, Kangawa K, Matsuo H, Matsukura S . Establishment of hypersensitive radioimmunoassay for islet amyloid polypeptide using antiserum specific for its N-terminal region. Biochem Biophys Res Commun. 1992; 186(2):1065-73. DOI: 10.1016/0006-291x(92)90855-f. View

Wang Z, Bennet W, Ghatei M, Byfield P, Smith D, Bloom S . Influence of islet amyloid polypeptide and the 8-37 fragment of islet amyloid polypeptide on insulin release from perifused rat islets. Diabetes. 1993; 42(2):330-5. DOI: 10.2337/diab.42.2.330. View

Cooper G, Willis A, Clark A, Turner R, Sim R, Reid K . Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci U S A. 1987; 84(23):8628-32. PMC: 299599. DOI: 10.1073/pnas.84.23.8628. View

Young A, Gedulin B, Greene H, Rink T, Cooper G . Amylin and insulin in rat soleus muscle: dose responses for cosecreted noncompetitive antagonists. Am J Physiol. 1992; 263(2 Pt 1):E274-81. DOI: 10.1152/ajpendo.1992.263.2.E274. View

Hartter E, Svoboda T, Ludvik B, Schuller M, Lell B, Kuenburg E . Basal and stimulated plasma levels of pancreatic amylin indicate its co-secretion with insulin in humans. Diabetologia. 1991; 34(1):52-4. DOI: 10.1007/BF00404025. View

Young A, CARLO P, Rink T, Wang M . 8-37hCGRP, an amylin receptor antagonist, enhances the insulin response and perturbs the glucose response to infused arginine in anesthetized rats. Mol Cell Endocrinol. 1992; 84(1-2):R1-5. DOI: 10.1016/0303-7207(92)90084-j. View

10.

Johnson K, OBrien T, Hayden D, Jordan K, Ghobrial H, Mahoney W . Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J Pathol. 1988; 130(1):1-8. PMC: 1880548. View

11.

Kassir A, Upadhyay A, Lim T, Moossa A, Olefsky J . Lack of effect of islet amyloid polypeptide in causing insulin resistance in conscious dogs during euglycemic clamp studies. Diabetes. 1991; 40(8):998-1004. DOI: 10.2337/diab.40.8.998. View

12.

Bevan S, Parry-Billings M, Opara E, Liu C, Dunger D, Newsholme E . The effect of insulin-like growth factor II on glucose uptake and metabolism in rat skeletal muscle in vitro. Biochem J. 1992; 286 ( Pt 2):561-5. PMC: 1132934. DOI: 10.1042/bj2860561. View

13.

Roden M, Liener K, Furnsinn C, Nowotny P, Hollenstein U, Vierhapper H . Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver. Diabetologia. 1992; 35(2):116-20. DOI: 10.1007/BF00402542. View

14.

Eriksson J, Nakazato M, Miyazato M, Shiomi K, Matsukura S, Groop L . Islet amyloid polypeptide plasma concentrations in individuals at increased risk of developing type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1992; 35(3):291-3. DOI: 10.1007/BF00400933. View

15.

Bretherton-Watt D, Gilbey S, Ghatei M, Beacham J, MACRAE A, Bloom S . Very high concentrations of islet amyloid polypeptide are necessary to alter the insulin response to intravenous glucose in man. J Clin Endocrinol Metab. 1992; 74(5):1032-5. DOI: 10.1210/jcem.74.5.1569151. View

16.

Leighton B, Cooper G . Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature. 1988; 335(6191):632-5. DOI: 10.1038/335632a0. View

17.

Westermark P, Wernstedt C, Wilander E, Hayden D, OBrien T, Johnson K . Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci U S A. 1987; 84(11):3881-5. PMC: 304980. DOI: 10.1073/pnas.84.11.3881. View

18.

Bhogal R, Smith D, Bloom S . Investigation and characterization of binding sites for islet amyloid polypeptide in rat membranes. Endocrinology. 1992; 130(2):906-13. DOI: 10.1210/endo.130.2.1310282. View

19.

Ohsawa H, Kanatsuka A, Yamaguchi T, Makino H, Yoshida S . Islet amyloid polypeptide inhibits glucose-stimulated insulin secretion from isolated rat pancreatic islets. Biochem Biophys Res Commun. 1989; 160(2):961-7. DOI: 10.1016/0006-291x(89)92529-1. View

20.

Morishita T, Yamaguchi A, Fujita T, Chiba T . Activation of adenylate cyclase by islet amyloid polypeptide with COOH-terminal amide via calcitonin gene-related peptide receptors on rat liver plasma membranes. Diabetes. 1990; 39(7):875-7. DOI: 10.2337/diabetes.39.7.875. View