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

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.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Aston University

Year dc:date.issued

1979

Author dc:creator

• Newton, David F.

DOI dc:identifier.doi

https://doi.org/10.48780/publications.aston.ac.uk.00010481

OAI identifier oai:identifier

oai:publications.aston.ac.uk:10481