No Sizable Inhibition of Glucose-Induced Insulin Secretion by Acarbose and Castanospermine

Introduction

Lundquist and co-workers proposed that one of the multiple signals implicated in glucose-induced insulin release is transduced through the vacuolar system involving the activation of lysosomal acid glucan-1,4-α-glucosidase [1] [2] [3] [4] [5] [6] [7]. In their view, this lysosomal enzyme attacks α-1,4-linked glucose polymers, such as glycogen, to produce high local concentrations of vacuolar glucose, which in turn might act as a metabolic, osmotic, or cybernetic messenger in insulin secretion. Their proposal was based on their findings of a close relationship between islet acid glucan-1,4-α-glucosidase activity and insulin secretion in a series of experiments with isolated islets, where 4 selective α-glucosidase inhibitors - miglitol [2], acarbose [3] [6] [7], emiglitol [4], and castanospermine [5] - suppressed glucose-induced insulin secretion in parallel with their inhibitory effect on islet glucan-1,4-α-glucosidase activity. No other investigators, however, have verified whether their proposal is valid or not. The aim of the present study was to assess the validity of their interesting view by examining the ability of acarbose and castanospermine to inhibit glucose-induced insulin secretion.

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