Abnormal insulin secretion in a streptozocin model of diabetes. Effects of insulin treatment.
We have proposed that chronic hyperglycemia causes the abnormal glucose influence on arginine-stimulated insulin secretion in the neonatal streptozocin (STZ) rat model of NIDDM and therefore studied the effect of 24 h of mild insulin-induced hypoglycemia on this defect. Ultralente insulin, 20 U/kg, was given at 9 a.m. and 10 U/kg at 5 p.m., and insulin and glucagon secretion were then studied the next morning using the in vitro isolated, perfused pancreas. The fed plasma glucose concentrations decreased in the STZ rats from 191 +/- 13 to 101 +/- 9 mg/dl and from 133 +/- 4 to 99 +/- 8 mg/dl in the controls. As expected, 10 mM arginine caused a trivial insulin response at 2.8 mM glucose in the treated and untreated control groups compared with the marked one at 16.7 mM. The response to arginine at 2.8 mM glucose in the untreated STZ rats, however, was strikingly elevated (7.65 +/- 2.29 versus 0.41 +/- 0.16 ng/ml in the untreated controls) and it was not potentiated by the high glucose background, but the result at 2.8 mM glucose in the treated STZ rats was similar to that of the treated controls (0.46 +/- 0.12 versus 0.16 +/- 0.03 ng/ml). A return of glucose influence on IBMX-stimulated insulin secretion was also noted. Glucose-induced insulin release, however, was not restored in the treated STZ rats, but it was markedly suppressed in the controls by the insulin treatment. Glucose influence on the glucagon response to arginine was maintained in the STZ model even though the glucagon release to a lowered glucose concentration was lost.(ABSTRACT TRUNCATED AT 250 WORDS)
J L
JL
Leahy
S
S
Bonner-Weir
G C
GC
Weir
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D001120:Arginine; D015056:1-Methyl-3-isobutylxanthine