Impaired phasic insulin and amylin secretion in diabetic rats.
We have proposed that a hyperstimulated insulin secretion causing beta-cell degranulation is the basis for the impaired glucose-potentiated insulin secretion in type 2 diabetes ("overworked beta-cell"). To confirm this idea, we previously investigated tolbutamide-infused euglycemic rats. Two novel kinds of beta-cell dysfunction were observed: altered phasic glucose-potentiated insulin secretion with preferential sparing of the first phase and a raised secreted ratio of amylin to insulin. The current study tested these parameters in 90% (intact beta-cell insulin stores) and 95% (markedly lowered insulin stores) pancreatectomized (Px) diabetic rats. Rats underwent pancreas perfusion 5-6 wk postsurgery. Controls showed nonchanging insulin secretion during a 20-min perfusion of 16.7 mM glucose + 10 mM arginine. In contrast, both Px groups showed an altered phasic pattern, with the first phase being supernormal (for the beta-cell mass) but the second phase reduced in tandem with the insulin content. Amylin secretion from control and 90% Px rats paralleled the insulin output, so that the amylin-to-insulin ratio averaged 0. 12 +/- 0.03% in the controls and 0.16 +/- 0.01% in the 90% Px rats over the two secretory phases. In contrast, the amylin-to-insulin ratio in 95% Px rats equaled that of controls during the first phase (0.12 +/- 0.1%) but was twice normal during the second phase (0.32 +/- 0.4%). These results confirm the validity of the overworked beta-cell schema by showing identical beta-cell functional defects in Px rats and tolbutamide-infused normoglycemic rats.
Leahy
J L
JL
Division of Endocrinology, Diabetes and Metabolism, University of Vermont, Burlington, Vermont 05405, USA.
Fineman
M S
MS
D000204:Activity Cycles; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010180:Pancreatectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000494:pharmacology
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D001120:Arginine; D014044:Tolbutamide; D005947:Glucose