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

Summary

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.

Abbreviations

DTT:

Dithiothreitol

TLCK:

tosyl lysyl chloromethyl ketone

GSPase:

glycogen synthase phosphatase

G3PAT:

glycerol-3-phosphate acyl transferase

G/K:

Goto-Kakizaki rat

IPG:

Inositolphosphoglycan

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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