How does glibenclamide lower plasma glucose concentration in patients with type 2 diabetes?

Twelve patients with Type 2 diabetes and uncontrolled hyperglycaemia, never before treated with anti-diabetic drugs, were studied before and after several months of glibenclamide therapy. Fasting plasma glucose fell significantly (p less than 0.01) from 12.5 +/- 1.1 (mean +/- SE) to 8.3 +/- 0.4 mmol l-1 with glibenclamide therapy, as did glycosylated haemoglobin (from 12.0 +/- 0.9 to 8.4 +/- 0.7%). The improvement in blood glucose control was accompanied by an increase in postprandial plasma insulin concentration measured hourly from 0800 to 1600 h (p less than 0.001). Over the same period, plasma NEFA and lactate levels were significantly (p less than 0.001) lower after treatment with glibenclamide. Mean (+/- SE) insulin-mediated glucose metabolic clearance rate was evaluated during glucose clamp studies, and was significantly higher (p less than 0.001) after glibenclamide therapy at steady-state insulin levels of approximately 10 mU l-1 (53 +/- 3 vs 38 +/- 2 ml-2 min-1) and approximately 70 mU l-1 (78 +/- 9 vs 55 +/- 6 ml m-2 min-1). Hepatic glucose production was also lower following glibenclamide treatment at both the lower (56 +/- 5 vs 68 +/- 5 mg m-2 min-1) and higher 22 +/- 4 vs 32 +/- 6 mg m-2 min-1) insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)