Mechanism of Improvement in Glucose Metabolism After Chronic Glyburide Therapy

Abstract

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 less than 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 X min, P = NS) and was positively correlated with the fasting glucose concentration (r = 0.93, P less than 0.001). With chronic glyburide therapy, HGP declined to 1.72 mg/kg X min (P less than 0.01 versus preglyburide) and remained highly correlated with the fasting glucose concentration (r = 0.85, P less than 0.005). Basal glucose clearance in NIDDM was reduced by 48% compared with age-matched controls (1.22 versus 2.32 ml/kg X min, P less than 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 X min, P less than 0.001). After glyburide, insulin-mediated glucose metabolism increased by 26% to 3.67 mg/kg X min (P less than 0.01). This increase in tissue sensitivity to insulin was unassociated with any change in insulin binding to monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

KATP channelopathies in the pancreas

“…In addition, glucose metabolites and incretins (e.g., glucagon-like-peptide-1, GLP1) can affect secretion at various stages downstream of K ATP [14,28,38,54]. Nevertheless, the ability of highly selective K ATP drugs (KCOs and inhibitory SU drugs) to modulate GSIS both in vivo and in vitro underscores the central role of K ATPdependent regulation [117,130].…”

Quantitation of basal endogenous glucose production in Type II diabetes: importance of the volume of distribution

“…4 (see also Table 2). The calculated R d is now greater than R a , so that R a -R d is negative, providing the drive which decreases C [for example see the first of the equations (14)]. There is a definite decrease in the calculated R a , which however, continues to appear high, particularly in the first several hours of the study in diabetic subjects (Fig.…”

“…Impaired hepatic uptake would also increase net splanchnic production [1,9,11,13]. Nevertheless, other investigators [14,15,16,17,18,19] concluded that glucose production is altered only marginally during fasting hyperglycaemia and changes substantively only when there is a high increase of glucose concentrations. The discussion centred largely on the methodology.…”

“…It is usually considered to be less than one since glucose appears in the circulation, where it is measured, and its concentrations would therefore be highest at this site. R d , the rate of glucose utilisation or disappearance, can then be calculated from: (14) This calculation is exemplified by panels C2 and F2 of Fig. 4 (see also Table 2).…”

The use of oral antidiabetic medications in gestational diabetes mellitus

“…They generally lower circulating glucose levels by approximately 20% and work best in patients of normal or slightly increased body weight. It has also been shown that sulfonylureas can enhance peripheral tissue sensitivity to insulin [7][8][9]. Glyburide, a second-generation sulfonylurea, was initially demonstrated not to cross the placenta in signifi cant amounts and fetal concentrations reached no more than 1% to 2% of maternal concentrations [10][11][12].…”