Mechanism of improvement in glucose metabolism after chronic glyburide therapy

D. C. Simonson, E. Ferrannini, S. Bevilacqua, D. Smith, E. Barrett, R. Carlson, R. A. DeFronzo

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


The effect of glyburide on glucose metabolism was examined in 10 non-insulin-dependent diabetic subjects (NIDDM) and 7 young, control subjects. After 3 mo of glyburide treatment in NIDDM, fasting plasma glucose declined from 198 to 141 mg/dl (P < 0.01) without change in fasting insulin levels. Basal hepatic glucose production (HGP) was slightly elevated in NIDDM versus controls (2.35 versus 2.18 mg/kg·min, P = NS) and was positively correlated with the fasting glucose concentration (r = 0.93, P < 0.001). With chronic glyburide therapy, HGP declined to 1.72 mg/kg·min (P < 0.01 versus preglyburide) and remained highly correlated with the fasting glucose concentration (r = 0.85, P < 0.005). Basal glucose clearance in NIDDM was reduced by 48% compared with age-matched controls (1.22 versus 2.32 ml/kg·min, P < 0.001) and was unchanged after 3 mo of glyburide. Thus, the most important factor responsible for the decline in fasting plasma glucose concentration was an inhibition of hepatic glucose output. The decrease in basal hepatic glucose production and fasting plasma glucose concentration occurred without any change in fasting plasma insulin or C-peptide concentration. Insulin-mediated glucose metabolism (insulin clamp technique) was reduced by 55% in NIDDM (2.91 versus 6.39 mg/kg·min, P < 0.001). After glyburide, insulin-mediated glucose metabolism increased by 26% to 3.67 mg/kg·min (P < 0.01). This increase in tissue sensitivity to insulin was unassociated with any change in insulin binding to monocytes. Beta cell secretion of insulin (hyperglycemic clamp technique) was markedly impaired in NIDDM (mean plasma insulin response: 24 versus 54 μU/ml, P < 0.001). After glyburide, the plasma insulin response increased to 36 μU/ml (P < 0.01). These results indicate that improved glucose tolerance in NIDDM after glyburide results from both enhanced tissue sensitivity to insulin and increased insulin secretion. Glyburide administration to young, healthy, control subjects also increased insulin-mediated glucose metabolism (from 6.45 to 7.61 mg/kg·min, P < 0.05) without any change in insulin binding to monocytes. Insulin secretion, however, was unaltered. Thus, the primary mechanism responsible for the improvement in glucose metabolism in young controls was enhanced tissue sensitivity to insulin.

Original languageEnglish (US)
Pages (from-to)838-845
Number of pages8
Issue number9
StatePublished - 1984
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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