Evolution of abnormal insulin secretory responses during 48-h in vivo hyperglycemia.
Recent in vitro studies have shown that insulin release caused by continuous exposure to high glucose concentration markedly falls within a few hours. We wanted to determine if a similar effect occurs in vivo with chronic intravenous infusions in normal rats. Male CD rats (200-250 g) were infused with 50% glucose at 2 ml/h for 6, 14, 24, or 48 h, whereas controls received 0.45% NaCl, and insulin responses were tested with the in vitro isolated perfused pancreas. Plasma glucose averaged 352 +/- 20 mg/dl after 4 h and 396 +/- 11 mg/dl after 24 h versus 137 +/- 5 mg/dl in controls; plasma insulin at the same times was 8.94 +/- 1.44 and 12.1 +/- 2.62 ng/ml versus 1.69 +/- 0.19 ng/ml in controls. The incremental insulin response caused by an increase in perfusate glucose from 2.8 to 16.7 mM was not significantly reduced after 24 h of glucose infusion; in contrast, paradoxical suppression was seen after 48 h. A second protocol examined glucose potentiation by giving 10 mM arginine at 2.8 and 16.7 mM glucose; a hyperresponse to arginine at the lower glucose level was present after just 14 h of infusion. Therefore, these results do not support the hypothesis that beta-cells lose their sensitivity to glucose within hours of being exposed to higher than normal glucose concentrations.
Leahy
J L
JL
Research Division, Joslin Diabetes Center, Boston, MA 02215.
Weir
G C
GC
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D005934:Glucagon / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D009994:Osmolar Concentration; D010477:Perfusion; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D001120:Arginine