Abstract
In order to characterize the glucoreceptor mechanism involved in insulin release and the character of the release, we have studied dynamics of insulin release from the rat pancreas perfused with excess K+ media containing glucose, α-or β-methyl-D-glucopyranoside (α-MDG or βMDG). The results are as follows.
1. Perfusion in raising the extracellular K+ concentration from 6.2 to 24.8 mM
K+ (24.8 mM) provoked a transient enhancement of insulin release. The average rate of insulin release during the first 6-min period (the rate of insuln release) and the maximal value were 115 ± 11, μU/ml/min and 191 ± 17 μU/ml. respectively. The rate of insulin release by 2.8 mM glucose was 1.4 times as largeas that of the control. Insulin releasing profile due to 15.5 mM α-MDG was similar to that induced by 2.8 mM glucose, while insulin response dul to 15.5 mM β-MDG was below that of the control. Therefore, α-MDG specifically enhanced insulin release in a 24.8 mM K+ medium.
2. Perfusion in raising the extracellular K concentration from 6.2 to 12.4 mM
K+ (12.4 mM) did not enhance insulin release, and the rate of insulin release was only 22 ±8 μU/ml/min. The rate of insulin release and the maximal value caused by 2.8 mM glucose, which were indicated as 49 ± 10 μU/ml/min and 64 ± 22 μU/ml respectively, were significantly higher than those of the control experiment, but were lower than those by 2.8 mM glucose in a 24.8 mM K+ medium. The rate of insulin release by 15.5 mM α-MDG, which was indicated as 102 ± 26 μU/ml/min, was significantly higher than that of the control, but 15.5 mM α-MDG did not induce insulin release. Combined infusion of 2.8 mM glucose and 15.5 mM α-MDG or β-MDG caused almost the same insulin releasing profile as that due to α-or β-MDG. Therefore, both agents seemed to bind a glucoreceptor. In the presence of 12.4 mM K+, unlike in a 24.8 mM K+ medium, β-MDG specifically release insulin.
3. Perfusion in raising a extracellular K+ concentration from 6.2 to 12.4, and finally to 24.8 mM
K+ (24.8 mM) provoked a transient enhancement of insulin release. The rate of insulin release and the maximal value were 84 ±8 μU/ml/min and 153 ± 26 μU/ml. The rate of insulin release by 2.8 mM glucose was 2.6 times as large as that of the control and that by 15.5 mM μ-MDG, which was indicated as 159 ± 28 μU/ml/min, was significantly higher than that by 15.5 mM α-MDG, which was similar to that of the control. Combined infusion of 2.8 mM glucose and 15.5 mM α-MDG or β-MDG caused almost the same insulin releasing profile as that due to α-or β-MDG alone. Therefore, both agents seemed to bind a glucoreceptor. In the presence of 24.8 mM K+ raised from 12.4 mM K+, 43-MDG insulin release was specifically enhanced.
The results have led to the suggestion that the B cell may contain glucoreceptors on tne plasma membrane directly controlling insulin release, and moreover, that β-MDG with β configuration could interact with a glucoreceptor to cause insulin release through a change in a glucoreceptor conformation.
