Enzyme Inducers Improve Insulin Sensitivity in Non-insulin-dependent Diabetic Subjects

Abstract

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 < 0.01) and immunoreactive insulin (IRI) levels (from 32.4 ± 13.6 to 24.7 ± 9.8 mU/L, P < 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 < 0.001), the metabolic clearance rate of glucose (from 0.89 ± 0.41 to 2.24 ± 1.27 ml/kg/min, P < 0.01), the insulin sensitivity index (from 1.10 ± 0.44 to 2.86 ± 1.54 mg kg/min: mU/L × 100, P < 0.001), and the plasma antipyrine clearance rate (from 28.3 ± 11.7 to 51.4 ± 20.2 ml/min, P < 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 < 0.01). Thiscorrelation 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.