ABSTRACT

Corticosterone (0·6 μmol/l) inhibited both ⁴⁵Ca outflow and insulin release evoked by glucose, the combination of leucine and glutamine, 2-ketoisocaproate, gliclazide or the association of gliclazide and a tumour-promoting phorbol ester in rat pancreatic islets perifused at normal extracellular Ca²⁺ concentration (1·0 mmol/l). In all cases, the inhibitory action of corticosterone reached statistical significance within 10–22 min of exposure to this steroid and failed to be rapidly reversible. Corticosterone failed to affect basal ⁴⁵Ca outflow and insulin release. The steroid also failed to affect the inhibitory action of glucose upon ⁴⁵Ca outflow, as judged from either the glucose-induced early fall in effluent radioactivity from islets maintained at normal extracellular Ca²⁺ concentration or the steady-state values for ⁴⁵Ca outflow from glucose-stimulated but Ca²⁺-deprived islets. Corticosterone caused a modest increase in ⁸⁶Rb outflow from islets perifused in the presence of glucose (16·7 mmol/l). It is concluded that corticosterone impairs Ca²⁺ inflow into the islet cells and, by doing so, causes a progressive inhibition of insulin release. The pancreatic B cell might thus serve as a further model for the study of the rapid biological response to steroids, as presumably mediated by alteration in the biophysical properties of the plasma membrane.

J. Endocr. (1984) 100, 227–233

ABSTRACT

The direct effect of hypothermia on the inhibition of insulin secretion may result from inhibition of the availability of energetic substrates and/or the lack of metabolic signals. In order to verify this hypothesis, the insulin secretion and the main metabolic glucose pathways were measured during the incubation of rat islets. In the presence of 16·7 mmol glucose/l and at 37 °C, insulin secretion was 925 ± 119 μU/2 h per ten islets. With the same experimental conditions, glucose utilization, determined as the formation of ³H₂O from [5-³H]glucose was 2225 ±184 pmol/2 h per ten islets, glucose oxidation measured as the formation of ¹⁴CO₂ from [U-¹⁴C]glucose was 673 ± 51 pmol/2 h per ten islets, pentose cycle determined as the formation of ¹⁴CO₂ from either [1-¹⁴C]glucose or [6-¹⁴C]glucose was 37 ± 5 pmol/2 h per ten islets; glucose oxidation by the tricarboxilic acid cycle, calculated to be the difference between glucose oxidation and pentose cycle values, was 636 pmol/2 h per ten islets.

Hypothermia highly inhibited glucose-induced insulin secretion and glucose utilization. Inhibition of insulin secretion was partial at 27 °C since it was 2·5 times lower than that at 37 °C, and it was complete at 17 °C. Glucose oxidation in the tricarboxilic acid cycle was markedly inhibited by hypothermia since the inhibition coefficient (Q₁₀) between 37 and 27 °C was 5. In contrast, glucose oxidation in the pentose phosphate shunt was enhanced at 27 °C, reaching 92 ± 17 pmol/2 h per ten islets, and it was inhibited relatively little at 17 °C.

These results suggest that hypothermia markedly inhibits glucose metabolism with the exception of the pentose pathway which could play an important role by inducing the insulin secretion at 27 °C.

Journal of Endocrinology (1990) 125, 45–51

ABSTRACT

The direct effect of cold on the inhibition of B cell secretion is well known in hibernating and experimentally hypothermic mammals. This temperature dependency may result from the inhibition of ion transport across the membranes. In order to verify this hypothesis, ionic effluxes and insulin secretion from rat islets loaded with ⁸⁶Rb⁺ and ⁴⁵Ca²⁺ were measured during perifusion.

At 37 °C, the rise in glucose concentration from zero to 16·7 mmol/l provoked a rapid decrease in ⁸⁶Rb⁺ efflux, an early fall and subsequent rise in ⁴⁵Ca²⁺ efflux and a typical biphasic pattern of insulin secretion. At 27 °C, glucose induced only a very slight increase in insulin secretion, while the fluxes of radioactive ions were not significantly modified in amplitude but were clearly delayed. At 17 °C, no insulin response to glucose was observed and the decrease in K⁺ conductance indicated by ⁸⁶Rb⁺ flux decrease was less temperature-dependent than the movement of Ca²⁺. After supplementary stimulation with a high extracellular concentration of Ca²⁺, insulin secretion was enhanced at 27 °C and reached levels induced by glucose alone at 37 °C. An increase in hormone secretion occurred even at 17 °C, but only during a first phase of secretion.

Regular increases in temperature potentiated insulin secretion and provoked changes in ionic fluxes which suggest that B cell depolarization (⁸⁶Rb⁺ flux decrease) induced by glucose can occur at 15 °C but cannot induce the opening of voltage-dependent Ca²⁺ channels (increase in ⁴⁵Ca²⁺ efflux) until temperatures higher than 27 °C are reached.

These results suggest that cooling affects calcium movements especially rather than K⁺ conductance and insulin exocytosis per se.

J. Endocr. (1987) 115, 225–231