Prolonged hyperglycaemia during infusion of glucose and somatostatin impairs pancreatic A- and B-cell responses to decrements in plasma glucose in normal man: evidence for induction of altered sensitivity to glucose.
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 less than 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 less than 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.
Dimitriadis
G
G
Cryer
P
P
Gerich
J
J
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D004351:Drug Resistance; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D013004:Somatostatin; D013006:Growth Hormone; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone; D004837:Epinephrine