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Impaired skeletal muscle glycogen synthase activation by insulin in the Goto-Kakizaki (G/K) rat


The Goto-Kakizaki (G/K) rat is an animal model of non-insulin-dependent diabetes mellitus, with early hyperglycaemia, hyperinsulinaemia, and insulin resistance. We have studied the effect of insulin on the activation of glycogen synthase in the G/K rat and in the original parent strain, the Wistar rat. After insulin injection, glycogen synthase I activity, glycogen synthase phosphatase activity and glucose 6-phosphate content in skeletal muscle were significantly increased in the Wistar rats. In the G/K rats, insulin injection resulted in a reduced activation of skeletal muscle glycogen synthase, which was not significant when compared with the control rats without insulin, and no increases in glycogen synthase phosphatase and glucose 6-phosphate were seen. In adipose tissue the activation of glycogen synthase by insulin was normal in the G/K rats. Previous investigations have shown that glucose disappearance rates are low in the G/K rat. However, stimulation of glucose transport was reported to be normal in the G/K rat. A defective activation of glucose accumulation into glycogen by skeletal muscle may contribute to explain the hyperglycaemia in the G/K rat.





tosyl lysyl chloromethyl ketone


glycogen synthase phosphatase


glycerol-3-phosphate acyl transferase


Goto-Kakizaki rat




  1. 1.

    Goto Y, Kakizaki M, Masaki N (1975) Spontaneous diabetes produced by selective breeding of normal Wistar rats. Proc Jpn Acad 51: 80–85

  2. 2.

    Goto Y, Kakizaki M (1981) The spontaneous-diabetic rat: a model of non-insulin dependent diabetes mellitus. Proc Jpn Acad 57: 381–384

  3. 3.

    Yagihashi S, Tonosaki A, Yamada K-I, Kakizaki M, Goto Y (1982) Peripheral neuropathy in selectively-inbred spontaneously diabetic rats: electrophysiological, morphometrical and freeze-replica studies. Tohoku J Exp Med 138: 39–48

  4. 4.

    Kennington AS, Hill CR, Craig J et al. (1990) Low urinary chiro-inositol excretion in non insulin-dependent diabetes mellitus. New Eng J Med 323: 373–378

  5. 5.

    Ortmeter HK, Bodkin NL, Lilley K, Larner J, Hansen BC (993) Chiroinositol deficiency and insulin resistance I. Urinary excretion rate of chiroinositol is directly associated with insulin resistance in spontaneously diabetic rhesus monkeys. Endocrinology 132: 640–645

  6. 6.

    Suzuki S, Taneda Y, Hirai S et al. (1991) Molecular mechanism of insulin resistance in spontaneous diabetic GK (Goto-Kakizaki) rats. In: Sakamoto N, Angel A, Hotta N (eds) New directions in research and clinical works for obesity and diabetes mellitus. Elsevier Science, New York, pp 197–203

  7. 7.

    Larner J, Huang LC, Schwartz CF et al. (1988) Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphatase contains galactosamine and D-chiroinositol. Biochem Biophys Res Commun 151: 1416–1426

  8. 8.

    Machicao F, Mushack J, Seffer E, Ermel B, Haring HU (1990) Mannose, glucosamine, and inositol monophosphate inhibit the effects of insulin on lipogenesis. Biochem J 266: 909–916

  9. 9.

    Takeda Y, Brewer HB, Larner J (1975) Structural studies on rabbit muscle glycogen synthase. 1 Subunit composition J Biol Chem 250: 8943–8950

  10. 10.

    Villar-Palasi C (1991) Substrate specific activation by glucose 6-phosphate of the dephosphorylation of muscle glycogen synthase. Biochim Biophys Acta 1095: 261–267

  11. 11.

    Kornberg A (1950) Enzymatic synthesis of triphosphopyridine nucleotide. J Biol Chem 182: 805–813

  12. 12.

    Thomas JA, Schlender KK, Larner J (1968) A rapid filter paper assay for UDP-glucose-glycogen glucosyltransferase. Including an improved biosynthesis of UDP14C glucose. Anal Biochem 25: 486–499

  13. 13.

    Kato K, Bishop JS (1972) Glycogen synthase D phoshatase. I Some new properties of the partially purified enzyme from rabbit skeletal muscle. J Biol Chem 247: 7420–7429

  14. 14.

    Turinsky J, Bayly BP, O'Sullivan DM (1990) 1,2-Diacylglycerol and ceramide levels in rat skeletal muscle and liver in vivo. Studies with insulin, exercise, muscle denervation and vasopressin. J Biol Chem 265: 7933–7938

  15. 15.

    Kelley DE, Moran M, Mandarino LJ (1993) Metabolic pathways of glucose in skeletal muscle of lean NIDDM patients. Diabetes Care 16: 1158–1166

  16. 16.

    Khatra BS (1984) Properties of a phosphoprotein phosphatase from skeletal muscle and its regulation in diabetes. Proc Soc Exp Biol Med 177: 33–41

  17. 17.

    Kida Y, Esposito-Del Puente A, Bogardus C, Mott DM (1990) Insulin resistance is associated with reduced fasting and insulin stimulated glycogen synthase phosphatase activity in human skeletal muscle. J Clin Invest 85: 476–481

  18. 18.

    Bisbis S, Bailbe D, Tormo M-A et al. (1993) Insulin resistance in the GK rat: decreased receptor number but normal kinase activity in liver. Am J Physiol 265: E807-E813

  19. 19.

    Portha B, Serradas P, Bailbe D, Suzuki K-I, Goto Y, Giroix MH (1991) β-cell insensitivity to glucose in the GK rat, a spontaneous non-obese model for type II diabetes. Diabetes 40: 486–491

  20. 20.

    Ostenson C-G, Abdel-Halim SM, Rasschaert J et al. (1993) Deficient activity of FAD-linked glycerophosphate dehydrogenase in islets of GK rats. Diabetologia 36: 722–726

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Correspondence to Dr. C. Villar-Palasi.

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Villar-Palasi, C., Farese, R.V. Impaired skeletal muscle glycogen synthase activation by insulin in the Goto-Kakizaki (G/K) rat. Diabetologia 37, 885–888 (1994). https://doi.org/10.1007/BF00400943

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Key words

  • Glycogen synthase
  • insulin
  • Goto-Kakizaki rat
  • non-insulin-dependent diabetes mellitus
  • phosphatase
  • glucose 6-phosphate
  • skeletal muscle