Metabolism - Clinical and Experimental
Volume 44, Issue 6 , Pages 705-711 , June 1995

Amylin-mediated reduction in insulin sensitivity corresponds to reduced insulin receptor kinase activity in the rat in vivo

  • Michael Bryer-Ash

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Michael Bryer-Ash, MD, Department of Medicine SL-53, Tulane University Medical Center, 1430 Tulane Ave, New Orleans, LA 70112.
    • Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
    • Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA
  • ,
  • Lezley Follett

      Affiliations

    • Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
    • Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA
  • ,
  • Norman Hodges

      Affiliations

    • Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
    • Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA
  • ,
  • Sunil Wimalawansa

      Affiliations

    • Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
    • Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Medicine, University of Texas Medical Branch, Galveston, TX, USA

Received 26 June 1993 ,Accepted 3 October 1994.

References 

  1. Cooper GJS, Willis AC, Clark A, et al.  Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. In: ed 2. Proc Natl Acad Sci USA. 84:1987;p. 8628–8632
  2. Westermark P, Wernstedt C, Wilander E, et al.  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. In: ed 2. Proc Natl Acad Sci USA. 84:1987;p. 3881–3885
  3. Butler PC, Chou J, Carter WB, et al.  Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans. Diabetes. 1990;39:752–756
  4. Molina JM, Cooper GJS, Leighton B, et al.  Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide. Diabetes. 1990;39:260–265
  5. Sowa R, Sanke T, Hirayama J, et al.  Islet amyloid polypeptide amide causes peripheral insulin resistance in vivo in dogs. Diabetologia. 1990;33:118–120
  6. Hothersall JS, Muirhead RP, Wimalawansa S. The effect of amylin and calcitonin gene-related peptide on insulin-stimulated glucose transport in the diaphragm. Biochem Biophys Res Commun. 1990;169:451–454
  7. Leighton B, Cooper GJS. Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature. 1988;335:632–635
  8. Young DA, Deems RO, Deacon RW, et al.  Effects of amylin on glucose metabolism and glycogenolysis in vivo and in vitro. Am J Physiol. 1990;259:E457–E461
  9. Steiner DF, Ohagi S, Nagamatsu S, et al.  Is islet amyloid polypeptide a significant factor in pathogenesis or pathophysiology of diabetes?. Diabetes. 1991;40:305–309
  10. Johnson KH, O'Brien TD, Westermark P. Newly identified pancreatic protein islet amyloid polypeptide: What is its relationship to diabetes?. Diabetes. 1991;40:310–314
  11. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:E214–E223
  12. Burnol A, Leturque A, Ferre P, et al.  A method for quantifying insulin sensitivity in vivo in the anesthetized rat: The euglycemic insulin clamp technique coupled with isotopic measurement of glucose turnover. Reprod Nutr Dev. 1983;23:429–435
  13. Steele R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann NY Acad Sci. 1959;82:420–430
  14. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–254
  15. Bryer-Ash M. Rat insulin-receptor kinase activity correlates with in vivo insulin action. Diabetes. 1989;38:108–116
  16. Desbuquois B, Aurbach GD. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab. 1971;33:732–738
  17. Burant CF, Treutelaar MK, Buse MG. In vitro and in vivo activation of the insulin receptor kinase in control and denervated skeletal muscle. J Biol Chem. 1986;261:8985–8993
  18. Kasuga M, Fujita-Yamaguchi Y, Blithe DL, et al.  Characterization of the insulin receptor kinase purified from human placental membranes. J Biol Chem. 1983;258:10973–10980
  19. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–685
  20. Cooper JA, Hunter T. Changes in protein phosphorylation in Rous sarcoma virus-transformed chicken embryo cells. Mol Cell Biol. 1981;1:165–178
  21. Datta HK, Zaidi M, Wimalawansa SJ, et al.  In vivo and in vitro effects of amylin and amylin-amide on calcium metabolism in the rat and rabbit. Biochem Biophys Res Commun. 1989;162:876–881
  22. Nagamatsu S, Carroll RJ, Grodsky GM, et al.  Lack of islet amyloid polypeptide regulation of insulin biosynthesis or secretion in normal rat islets. Diabetes. 1990;39:871–874
  23. Broderick CL, Brooke GS, DiMarchi RD, et al.  Human and rat amylin have no effects on insulin secretion in isolated rat pancreatic islets. Biochem Biophys Res Commun. 1991;177:932–938
  24. Pettersson M, Ahren B. Failure of islet amyloid polypeptide to inhibit basal and glucose-stimulated insulin secretion in model experiments in mice and rats. Acta Physiol Scand. 1990;138:389–394
  25. Ghatei MA, Datta HK, Zaidi M, et al.  Amylin and amylinamide lack an acute effect on blood glucose and insulin. J Endocrinol. 1990;124:R9–R11
  26. Koopmans SJ, van Mansfeld ADM, Jansz HS, et al.  Amylin-induced in vivo insulin resistance in conscious rats: The liver is more sensitive to amylin than peripheral tissues. Diabetologia. 1991;34:218–224
  27. Zhu GC, Dudley DT, Saltiel AR. Amylin increases cyclic AMP formation in L6 myocytes through calcitonin gene-related peptide receptors. Biochem Biophys Res Commun. 1991;177:771–776
  28. Murad F, Brewer HB, Vaughan M. Effect of thyrocalcitonin on adenosine 3′:5′-cyclic phosphate formation by rat kidney and bone. In: ed 2. Proc Natl Acad Sci USA. 65:1970;p. 446–453
  29. Bryer-Ash M. Regulation of rat insulin-receptor kinase activity by glucose in vivo. Diabetes. 1991;40:633–640
  30. Kassir AA, Upadhyay AK, Lim TJ, et al.  Lack of effect of islet amyloid polypeptide in causing insulin resistance in conscious dogs during euglycemic clamp studies. Diabetes. 1991;40:998–1004
  31. Roden M, Liener K, Furnsinn C, et al.  Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver. Diabetologia. 1992;35:116–120
  32. Nishimura S, Sanke T, Machida K, et al.  Lack of effect of islet amyloid polypeptide on hepatic glucose output in the in situ—perfused rat liver. Metabolism. 1992;41:431–434
  33. Young AA, Cooper GJ, Carlo P, et al.  Response to intravenous injections of amylin and glucagon in fasted, fed, and hypoglycemic rats. Am J Physiol. 1993;264:E943–E950
  34. Frontoni S, Choi SB, Banduch D, et al.  In vivo insulin resistance induced by amylin primarily through inhibition of insulin-stimulated glycogen synthesis in skeletal muscle. Diabetes. 1991;40:568–573
  35. Furnsinn C, Nowotny P, Roden M, et al.  Insulin resistance caused by amylin in conscious rats is independent of induced hypocalcemia and fades during long-term exposure. Acta Endocrinol (Copenh). 1993;129:360–365
  36. Brain SD, Wimalawansa S, MacIntyre I, et al.  The demonstration of vasodilator activity of pancreatic amylin in the rabbit. Am J Pathol. 1990;36:487–490
  37. Young AA, Rink TJ, Wang MW. Dose response characteristics for the hyperglycemic, hyperlactemic, hypotensive and hypocalcemic actions of amylin and calcitonin gene-related peptide-I (CGRP alpha) in the fasted, anaesthetized rat. Life Sci. 1993;52:1717–1726

 Supported by a grant-in-aid from the Canadian Diabetes Association and the University Hospital Foundation, University Hospital, Vancouver, BC. M.B.-A, was the recipient of a scholarship from the British Columbia Health Research Foundation. L.F. was supported by a student research award from the Juvenile Diabetes Foundation Canada.

PII: 0026-0495(95)90181-7

Metabolism - Clinical and Experimental
Volume 44, Issue 6 , Pages 705-711 , June 1995