Drug-induced desensitization of insulin secretion

Introduction: Desensitization of insulin secretion is a reversible state of decreased secretory responsiveness of the endocrine pancreas after prolonged exposure to nutrient or non-nutrient stimuli. The underlying mechanisms are poorly understood inspite of their obvious relevance. Methods: Mouse islets were cultured for 20h in RPMI medium containing tolbutamide or the imidazoline efaroxan. Secretion was measured by perifusion and ELISA. KATP channel activity was measured by patch clamping, the cytosolic calcium concentration ([Ca2+]i) by microfluorometry. The insulin granule content was assessed by electron mic…