Impaired insulin secretion in human diabetes mellitus. Effect of pharmacological activation of gamma-aminobutyric acid system.
To evaluate whether the gamma-aminobutyric acid (GABA)ergic system plays a role in the defective insulin secretion in human diabetes mellitus, 15 non-insulin-dependent diabetics with fasting hyperglycemia above 140 mg/dl were submitted to two consecutive i.v. glucose tolerance tests (IVGTT) (0.33 g/kg b.w.), in basal conditions and after pharmacologic activation of the GABA system with baclofen and sodium valproate. Baclofen, a synthetic analogue, was given to 8 diabetics in two divided doses of 10 mg each 8h and 1h before the post-treatment test; sodium valproate, a drug that increases endogenous GABA activity, was given orally (800 mg) 60 min before the performance of the post-treatment IVGTT. Neither treatment brought about significant changes in insulin, C-peptide, glucagon or growth hormone responses to i.v. glucose nor did they significantly change glucose disappearance rates. These results seem to indicate that GABA does not play a major role in the pathogenesis of defective insulin secretion in non-insulin-dependent diabetes mellitus.
D000368:Aged; D001418:Baclofen / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D011963:Receptors, GABA-A; D014635:Valproic Acid; D001418:Baclofen