Abstract

Wistar fatty (WF) rats are obese, hyperinsulinemic and hyperglycemic, and thus a model of type 2 diabetes mellitus. Since we have found that insulin specifically inhibits glucagon-induced glycogenolysis in perivenous hepatocytes (PVH) from normal rats, we examined the inhibitory effect of insulin on glucagon-induced glycogenolysis in PVH of hyperinsulinemic WF rats. Basal glucose release was 64.0 ± 4.1 nmol/mg protein/30 min from PVH of lean littermates (WL rats) and 137.0 ± 19.3 nmol/mg protein/30 min from that of WF rats ( p < 0.01). These were proportional to the glycogen content in PVH of WL and WF rats (56.7 ± 7.2 and 131.0 ± 20.3 μg/mgprotein, p < 0.01), and increased to 109.0 ± 8.8 and 225.8 ± 17.9 nmol/mg protein/30 min, respectively, with 0.1 nmol/l glucagon. When 10 nmol/l insulin was coincubated, 0.1 nmol/l glucagon-induced increase in glucose release decreased to 93.3 ± 10.9 nmol/mg protein/30 min in PVH of WL rats ( p < 0.01) and to 181 ± 20.7 nmol/mg protein/30 min in PVH of WF rats ( p < 0.01). Thus, insulin antagonized glucagon-induced glycogenolysis in PVH similarly between WL and WF rats, to 56.7 ± 13.3% and to 46.1 ± 7.5%, respectively. Thus, the antagonizing effect of insulin on glucagon-induced increase in glycogenolysis was preserved in PVH of hyperinsulinemic and hyperglycemic WF rats.

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