Treatment of noninsulin-dependent diabetes mellitus with enzyme inducers

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Abstract
Although treated adequately with antidiabetic drugs, diet, exercise and education, patients with noninsulin-dependent diabetes mellitus (NIDDM) may develop resistance to treatment. In NIDDM hepatic microsomal enzyme activity is reduced and since postreceptional glucose metabolism is influenced by these enzymes, the subjects were treated with enzyme-inducing drugs. These inducers (phenobarbital and medroxyprogesterone acetate) when added as adjuvant therapy to a sulfonyl urea regimen, reduced blood glucose and plasma insulin, and increased microsomal enzyme activity (as indicated by increased antipyrine metabolism). A trial with placebo did not alter serum glucose levels. Body weight fell and serum aminotransferase levels were normalized. These changes were reflected by reduction of liver fat content (determined by light microscopy), by increased surface density of smooth endoplasmic reticulum and by reparation of the plasma cell membrane of hepatocytes, as seen by EM. Activation of postreceptional events in hepatocytes may thus be a new approach in the treatment of therapy-resistant type II diabetes.