Beta-cell dysfunction in hyperglycaemic rat models: recovery of glucose-induced insulin secretion with lowering of the ambient glucose level.
Glucose-induced insulin secretion is lost in the face of chronic hyperglycaemia. The same defect is present when normal rats are made hyperglycaemic by 48-h glucose infusions. Insulin secretory responses were mapped out during the post-infusion period in order to determine how long it takes for normal Beta-cell function to recover, and to identify factors which influence the rate of recovery. Male Sprague Dawley rats weighing 200-250 g were infused with 50% glucose or 77 mmol/l NaCl for 48 h. The glucose-infused rats were mildly hypoglycaemic for 14 h after the infusion ceased. Glucose-induced insulin secretion, absent at the end of the glucose infusion, was normal 6 h post-infusion. Such rapid recovery was not because of the short duration of hyperglycaemia; mild hypoglycaemia from a 5-h insulin infusion in 90% pancreatectomized rats resulted in a four-fold rise in glucose-induced insulin secretion. Under in vitro conditions, extreme glucose deprivation caused by perfusing the pancreas of glucose-infused rats with buffer devoid of glucose restored glucose-induced insulin secretion in just 37 min. Therefore, the suppression of glucose-induced insulin release by chronic hyperglycaemia is a dynamic situation that requires ongoing hyperglycaemia to prevent the reappearance of glucose responsiveness. This study shows recovery of glucose-induced insulin secretion after just 6 h of mild hypoglycaemia in vivo and even faster recovery with more severe glucose deprivation in vitro. Our results suggest that there is an inverse relationship between the rate of return of Beta-cell glucose responsiveness and the ambient glucose concentration.
Leahy
J L
JL
Research Division, Joslin Diabetes Center, Boston, Massachusetts.
Weir
G C
GC
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009929:Organ Size; D010180:Pancreatectomy; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D001120:Arginine; D005947:Glucose