Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects.
The reduction in blood glucose in non-insulin-dependent diabetes mellitus (NIDDM) brought about by the use of phenobarbital (PB), a hepatic microsomal enzyme inducer, suggests an improvement in insulin sensitivity. The effect of PB on insulin-mediated glucose metabolism was hence investigated using the euglycemic clamp technique in 10 women with NIDDM aged 56-75 yr. The addition of PB to sulfonylurea therapy, concurrently for 6 wk, reduced fasting blood glucose (BG, from 12.8 +/- 1.6 to 10.2 +/- 3.2 mmol/L, P less than 0.01) and immunoreactive insulin (IRI) levels (from 32.4 +/- 13.6 to 24.7 +/- 9.8 mU/L, P less than 0.01), whereas body weight remained unaltered. During the trial, there was a significant change in the glucose disposal rate (M, from 1.27 +/- 0.60 to 2.82 +/- 0.86 mg/kg/min, P less than 0.001), the metabolic clearance rate of glucose (from 0.89 +/- 0.41 to 2.24 +/- 1.27 ml/kg/min, P less than 0.01), the insulin sensitivity index (from 1.10 +/- 0.44 to 2.86 +/- 1.54 mg/kg/min: mU/L X 100, P less than 0.001), and the plasma antipyrine clearance rate (from 28.3 +/- 11.7 to 51.4 +/- 20.2 ml/min, P less than 0.001), an in vivo index of liver microsomal enzyme activity. The antipyrine clearance rate correlated with insulin-mediated glucose metabolism (r2 = 0.560, P less than 0.01). This correlation could be interpreted as indicating that, in NIDDM patients, peripheral glucose utilization and the liver microsomal enzyme system share common regulators. Our study suggests a new approach to the improvement of insulin sensitivity in NIDDM patients.
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008111:Liver Function Tests; D008875:Middle Aged; D010634:Phenobarbital / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D010634:Phenobarbital