Skeletal muscle glucose disposal after re-feeding in the hyperthyroid rat.

Experimental hyperthyroidism has been demonstrated to influence insulin-stimulated glucose utilization in isolated skeletal muscle preparations from fed or starved rats, with increased glycogen-glucose < 1 -phosphate cycling [ I ] and diversion of carbon from net glycogenesis (storage) to glycolysis (degradation) [2]. The present study investigated whether this effect of hyperthywidism is also observed in the intact animal under physiological conditions associated with hyperinsulinaemia and skeletal muscle glycogen deposition, namely refeeding after prolonged (48 h) starvation. Effects of experimental hyperthyroidism o n concentrations of fructose 2,6-bisphosphate [Fru( 2,6)P2], an allosteric activator of glycolysis, were also examined. Two representative hindlimb skeletal muscles: soleus (type 1, oxidative, working in the resting state) and gastrocnemius (type 2. mixed oxidative/ glycolytic. non-working in the resting state), were chosen for study. Comparison was made with changes in glycogen and Fru( 2,6)/’, concentrations in the heart, which is known to exhibit profound changes in contractile activity and metabolism in hyperthyroidism. Albino Wistar rats were either starved for 48 h or starved for 48 h and then refed chow (52% carbohydrate; 16%) protein: 2% lipid, w / ~ ) ud lihitirm, sampling after 2. 4, 6, X or 24 h of refeeding. One group o f rats was injected with triiodothyronine (100 &day per 100 g body weight) for 3 days, sampling on day 3 (see [3]). Muscles were freeze clamped while the rats were under pentobarbital anaesthesia (5 min; 6 mg/ 100 g body wt.). Glycogen and Fru( 2,6)P2 concentrations were measured in extracts of freeze-clamped muscles as described previously [4]. Basal (48 h starved) glycogen concentrations were significantly lower in the soleus than in the gastrocnemius, whereas Fru( 2,6)P, concentrations were higher in soleus (compare Figs. l a and lh) . Hyperthyroidism had no effect on basal (48 h starved) glycogen or Fru(2,6)Pz concentrations in either skeletal muscle (Figs. 1 a and 1 h). The initial rate of glycogen repletion was significantly higher in the soleus than in the gastrocnemius (compare Figs. I u and 1 h). This is likely to be related to the significantly lower basal glycogen concentration which is observed in the