The effect of glyburide on beta-cell sensitivity to glucose-dependent insulinotropic polypeptide.
OBJECTIVE
To assess whether treatment with glyburide alters beta-cell sensitivity to GIP in NIDDM patients.


METHODS
We studied 5 untreated NIDDM patients in a meal study (Ensure, 240 ml/M2) and a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above fasting). From 60 to 120 min of the clamp, GIP was infused in a primed continuous manner at a rate of 2 pmol.kg-1 x min-1. Subjects then were treated with glyburide. After they had been on a stable dose of medication for 1 mo, the meal study and glucose clamp studies were repeated.


RESULTS
In response to treatment, a decrease in fasting glucose and an increase in weight was observed (12.8 +/- 1.8 vs. 8.5 +/- 0.8 mM and 74.3 +/- 6.3 vs. 76.1 +/- 6.3 kg, respectively, P < 0.05). In response to the meal study, the AUC for glucose was less, for insulin was increased, and for GIP was unchanged after treatment (16.9 +/- 2.1 vs. 12.6 +/- 6.9 mM, P < 0.05; 161 +/- 47 vs. 242 +/- 60 pM, P < 0.05; and 199 +/- 22 vs. 219 +/- 18 pM, respectively). During the hyperglycemic clamp, steady-state glucose and 90- to 120-min GIP values were equivalent before and after treatment (18.0 +/- 1.3 vs. 18.3 +/- 1.3 mM and 302 +/- 59 vs. 298 +/- 37 pM, respectively). The 90-120 min insulin responses to the hyperglycemic clamp were greater after therapy (123 +/- 37 vs. 283 +/- 80 pM, P < 0.05) reflecting increased beta-cell responses to GIP.


CONCLUSIONS
We conclude that glyburide enhances beta-cell sensitivity to GIP.
Meneilly
G S
GS
Department of Medicine, University of British Columbia, Vancouver, Canada.
Bryer-Ash
M
M
Elahi
D
D
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004435:Eating; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D005905:Glyburide