Model of synthesis and release of insulin from rat islet β-cells and the effect of pretreatment with tolbutamide

Abstract

A kinetic model involving synthesis of proinsulin in the rough endoplasmic reticulum, maturation through the Golgi apparatus and granules, with conversion to insulin, is proposed to account for data on the amount of insulin and of proinsulin both secreted during various time intervals and remaining in islets. Introducing three compartments for granules makes it possible to account for the measurement of both hot (pulse labeled with tritiated leucine) and cold proinsulin and insulin over a period of 21/2 hr under constant glucose. Data from islets from animals pretreated with tolbutamide are also presented and modeled. The model is then expanded so that it can be successfully applied to available data on the effects of a period of glucose deprivation on secretion of both hot and cold hormone. Parameters have essentially the same values, where they overlap, as were obtained (Landahl and Grodsky, 1982Bull. math. Biol. 44, 399–410) from insulin secretion by perfused rat pancreas stimulated by a variety of temporal patterns of glucose concentration.