The Glucose Sensitivity of Insulin Secretion-Lessons from In Vivo and In Vitro Studies in Mice

Abstract

This study explored the relationship between the glucose dose and insulin response from beta cells in vivo and in vitro in mice. Glucose was administered intravenously at different dose levels (from 0 to 0.75 g/kg) in anesthetized C57BL/6J mice, and the glucose and insulin concentrations were determined in samples taken after 50 min. Furthermore, freshly isolated mouse islets were incubated for 60 min in the presence of different concentrations of glucose (from 2.8 to 22.2 mmol/L) and insulin levels were analyzed in the medium. It was found that insulin levels increased after an intravenous injection of glucose with the maximal increase seen after 0.35 g/kg with no further increase after 0.5 or 0.75 g/kg. The acute increase in insulin levels (during the first 5 min) and the maximum glucose level (achieved after 1 min) showed a curvilinear relation with the half-maximal increase in insulin levels achieved at 11.4 mmol/L glucose and the maximal increase in insulin levels at 22.0 mmol/L glucose. In vitro, there was also a curvilinear relation between glucose concentrations and insulin secretion. Half maximal increase in insulin concentrations was achieved at 12.5 mmol/L glucose and the maximal increase in insulin concentrations was achieved at 21.5 mmol/L. Based on these data, we concluded that the glucose-insulin relation was curvilinear both in vivo and in vitro in mice with similar characteristics in relation to which glucose levels that achieve half-maximal and maximal increases in insulin secretion. Besides the new knowledge of knowing these relations, the results have consequences on how to design studies on insulin secretion to obtain the most information.