Studies on the Effects of Growth Hormone and Thyroxine on Proinsulin Synthesis and Insulin Formation in the Isolated Islets of Langerhans of the Rat

By using pulse-chase and islet-fractionating techniques, proinsulin synthesis and insulin formation in isolated islets from normal and hypophysectomized (Hx) rats have been studied. In both groups of rat islets, proinsulin synthesis took place in the microsomal fraction and its conversion to insulin in the granular fraction (which includes the Golgi complex). The total incorporation of 3H-leucine into proinsulin and insulin in the islets from Hx rats during the 30 min period of pulsing was 48% of the value obtained in the normal islets from control rats. When growth hormone (GH) was added to the incubation medium for islets from Hx rats, a substantial increase (79% of that found in normal islets) in total incorporation of 3H-leucine into proinsulin and insulin was observed. When the incubation mixture was supplemented with thyroxine (THY) along with growth hormone, the conversion of proinsulin to insulin was increased during the pulsing and chasing periods. The enhancement of insulin biosynthesis as a result of both GH and THY was confirmed by straight pulsing experiments. The possible mechanisms for the enhanced effect are discussed.