CHANGES INDUCED BY HYPOTHYROIDISM IN INSULIN-SECRETION AND IN THE PROPERTIES OF ISLET PLASMA-MEMBRANES

This work was aimed at elucidating the effect of thyroid function on the physiology and biochemistry of the islet-cell population within the endocrine pancreas. To this end, we performed a comparative study of the physicochemical properties of islet-cell membranes and of the dynamics of glucose-induced insulin secretion in isolated pancreatic islets prepared from euthyroid i.e. control (C), hypothyroid (H), and thyroxin-supplemented hypothyroid (HT) rats. H rats were obtained by injecting normal rats with iodine-131, while HT rats consisted of H rats treated with thyroxin (T4). Insulin secretion was studied in isolated islets perifused with 3.3 and 16.6 mM glucose. Physicochemical properties of the partially purified islet plasma membranes were assessed by measurements of fluorescence polarization with the fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH) as a lipidic molecular probe. Insulin output during either the first or second phase of insulin secretion in H islets was significantly lower than in C islets. The slope of the curve in the second phase of insulin secretion was also lesser in H than in C islets, suggesting an additional defect in their velocity of hormone release. T4 administration of H rats reversed the decrease in insulin output to the range found in C islets but was incapable of correcting the defect in the hormone-secretion velocity. Several changes were found in the physicochemical properties of the membranes obtained from H islets as compared to C islets. There was an increase in the membrane-lipid-microviscosity values (eta), a smaller modification of phase-transition values in response to changes in temperature, lower flow-activation-energy (DELTAE) values below and above the temperature-dependent phase transition (T(t) and a lack of DELTAE changes after islet incubation with glucose. These differences would indicate that islet membranes in H animals exhibit an increase both in their microviscoity i.e. a decrease in their microfluidity and in the degree of order of their lipid bilayer as well as a decrease in their capacity to undergo changes in DELTAE in response to glucose. T4 administration reversed the majority of these alterations. These results suggest that changes in the physicochemical properties of the islet membranes induced by hypothyroidism - especially with respect to lipid composition and microviscosity - could account, at least to some extent, for the decreased amount and lower velocity of H islets in the release of insulin in response to glucose. In addition, these results emphasize the modulatory function of thyroid hormones in this fundamental pancreatic process.