The influence of proinsulin upon glucose uptake in rat skeletal muscle

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Bielen, Frieda V.
Craig, Bruce W.
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Thesis (M.A.)
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The effect of Biosynthetic Human Proinsulin on glucose uptake by skeletal muscle was studied in the isolated perfused hindquarter of fasted rats. Animals were randomly assigned to the control group, insulin-perfused or proinsulin-perfused group. Glucose disappearance from the perfusate and muscle glycogen levels before and after 2 hours perfusion were measured. Perfusate glucose concentration showed the greatest decline in the insulin group, which was significantly lower (p < .01) than control from 60 to 120 min. Proinsulin perfusion resulted in a smaller and delayed decrease in perfusate glucose. The proinsulin perfusate glucose levels were significantly higher (p < .05) than the insulin glucose values during the second hour of perfusion. After the first hour of perfusion, insulin infusion resulted in higher rates of glucose uptake than control (p < .005) or proinsulin infusion (p < .05). The glucose uptake by muscles perfused with proinsulin was significantly different from control values only at the 2 hour time point (p < .05). Glycogen concentration following insulin infusion increased significantly in the oxidative muscles, i.e. soleus (p < .05) and red vastus (p < .002). These increases in glycogen were significantly different from the changes observed in muscles of control animals. The plantaris and white vastus muscles, which have fast twitch fibers, did not show a significant response to insulin. Proinsulin perfusion decreased glycogen levels regardless of the muscle type. This decline was significantly different from the glycogen changes in soleus (p < .025), plantaris (p < .001) and white vastus (p < .05) muscles of control animals. The proinsulin glycogen fall was also significantly different from the insulin induced response in soleus, plantaris and red vastus muscles (p < .001). These results show that proinsulin has 8.6 % of the biologic potency of insulin for glucose uptake in rat skeletal muscle. Insulin induced an increase in glycogen concentration in oxidative muscles, but proinsulin elicted a drop in glycogen level regardless of the muscle type.