Stimulation of insulin release by isosmolar addition of permeant molecules

Abstract

Pancreatic β-cells are known to respond to hyposmolar stress by releasing insulin. It was evident from perifusion studies using islet cells from oblob-mice mixed with polyacrylamide beads that a similar type of secretory response can be obtained by isosmolar addition of 10–25 mM of the rapidly penetrating urea molecule. There was no effect with hyperosmolar addition of urea. The urea-induced insulin release differed from the ordinary stimulation of secretion in not disappearing but being more pronounced after previous heating to 45°C or removal of extracellular Ca²⁺. Isosmolar urea was exceptional as an insulin secretagogue in being effective also in the presence of the α₂-adrenergic agonist clonidine or when lowering the temperature to 24°C. Further support for the idea that isosmolar addition of rapidly penetrating molecules induces insulin release was obtained by test ing non-metabolizable glucose analogues. Whereas 25 mM 3-O-methyl-D-glucose doubled the secretory rate within 4 min, the non-permeant L-glucose had only a slight initial action. When not compensating for the alterations of the medium osmolarity 3-O-methyl-D-glucose was without effect. Although expansion of β-cells cannot explain the existence of a pronounced initial secretory response to D-glucose it may under certain conditions contribute to the stimulatory effects of the sugar.