A Study of Glucose Stimulus Insulin Secretion Coupling using Lean and Obese Mouse Islets of Langerhans

Abstract

Glucose-stimulus insulin secretion coupling has been investigated using isolated islets of Langerhans from lean homozygous (+/+) and genetically obese hyperglycaemic (ob/ob) mice. Streptozotocin inhibition of the insulin response to glucose but not glucagon suggests glucose sensitive sites and adenylate cyclase systems to be separate physiological entities at the level of the B-cell membrane.

Perifusion of islets with gradients of mutarotated and the anomeric forms of D-glucose in the presence of phloridzin and the insulin response of islets bound to lectin suggests that lean mouse islets recognise glucose as the stimulus for insulin secretion via a B-cell membrane glucoreceptor that shows a preferential affinity for a-D-glucose. -D-glucose is preferentially transported into the B-cell to maintain the insulin response.

The sensitivity of obese mouse islet membrane glucoreceptors to a-D-glucose is reduced and insulin secretion in this case depends upon a greater contribution from that part of the receptor sensitive to B-D-glucose.

Studies using 24-hour fasted animals demonstrated that the integrity of glucoreceptor sensitivity depended upon the nutritional status of the animal. Glucoreceptor sensitivity and the characteristic insulin response of lean mouse islets to a-D-glucose develops with age (4-5 weeks). Neonatal mouse islets provide little insulin response to glucose but a prominent response to certain amino acids.

A model for glucose-stimulus insulin secretion coupling has been proposed and it is suggested that reduced glucoreceptor sensitivity of obese mouse islets contributes to the manifestation of the obese hyperglycaemic syndrome.

Date of Award	1979
Original language	English
Awarding Institution	Aston University