Influence of gliclazide on glucose-stimulated insulin release in man.
Although sulfonylureas (SU) are widely used in the management of patients with non-insulin-dependent diabetes mellitus (NIDDM), there is still debate about their mechanism of action on the pancreatic beta cell. It is unclear whether the effect of SU on insulin release is additive to the effect of glucose, or whether SU act by increasing pancreatic beta-cell sensitivity to glucose (a shift in the dose-response curve of glucose-stimulated insulin release without a change in maximum release). To address this issue, we assessed the influence of the SU gliclazide on glucose-stimulated insulin release in eight healthy male volunteers. Sixty-minute hyperglycemic glucose clamps (blood glucose levels: 8 mmol/L, a submaximal stimulus; and 32 mmol/L, a maximally stimulating concentration) were performed with and without prior oral administration of gliclazide (80 mg) 30 minutes before the glucose clamp. Mean plasma C-peptide increment at 5 minutes (first-phase secretion) obtained during the 8-mmol/L hyperglycemic clamp, was higher on the gliclazide study day than on the control day (1.07 +/- 0.10 v 0.88 +/- 0.10 mmol/L, P less than .05), whereas no difference in plasma C-peptide response was observed during the 32-mmol/L hyperglycemic clamp. Mean plasma C-peptide increment obtained at the end 60 minutes; (second-phase secretion) of the 8-mmol/L hyperglycemic clamps was higher on the gliclazide study day than on the control day (1.36 +/- 0.13 v 1.09 +/- 0.09 mmol/L, P less than .02). No difference was observed in plasma C-peptide response at the end of the 32-mmol/L hyperglycemic glucose clamps.(ABSTRACT TRUNCATED AT 250 WORDS)
van Haeften
T W
TW
Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
Veneman
T F
TF
Gerich
J E
JE
van der Veen
E A
EA
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D005907:Gliclazide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005907:Gliclazide; D005947:Glucose