To determine the effects of prolonged hyperglycaemia on pancreatic islet A- and B-cell function, plasma glucose was clamped for 12 h at approximately 11 and 5 mmol/l in control experiments by infusing glucose and somatostatin along with replacement amounts of insulin, glucagon, and growth hormone in seven normal volunteers. Following restitution of euglycaemia for 1 h after prolonged hyperglycaemia, termination of the somatostatin-replacement hormone infusions resulted in a sustained decrease in plasma glucose to 3 mmol/l (p<0.01). Despite this, plasma glucagon did not increase above values observed in control experiments in which plasma glucose did not decrease; moreover, there was a persistent increase in insulin secretion nearly threefold above that observed in control experiments (p<0.01). Plasma growth hormone, cortisol and adrenaline responses were appropriate. This failure of a decrement in plasma glucose to suppress insulin secretion and to stimulate glucagon secretion was not observed when comparable hypoglycaemia was induced by exogenous insulin after a prolonged euglycaemic clamp. Our results indicate that hyperglycaemia can induce altered sensitivity of pancreatic A and B cells to glucose and suggest that abnormal A- and B-cell responses to glucose in diabetes mellitus may not represent a wholly intrinsic defect.
- A cell
- B cell