BACKGROUND and METHODS. Inositol is a major component of the intracellular mediators of insulin action. To investigate the possible role of altered inositol metabolism in non-insulin-dependent diabetes mellitus (NIDDM), we used gas chromatography and mass spectrometry to measure the myo-inositol and chiro-inositol content of urine specimens from normal subjects and patients with NIDDM. The study subjects were whites, blacks, and Pima Indians. The type of inositol and its concentration in insulin-mediator preparations from muscle-biopsy specimens from normal subjects and diabetic patients were also determined. RESULTS. The urinary excretion of chiro-inositol was much lower in the patients with NIDDM (mean [+/- SE], 1.8 +/- 0.8 mumol per day) than in the normal subjects (mean, 84.9 +/- 26.9 mumol per day; P less than 0.01). In contrast, the mean urinary myo-inositol excretion was higher in the diabetic patients than in the normal subjects (444 +/- 135 vs. 176 +/- 46 mumol per day; P less than 0.05). There was no correlation between chiro-inositol excretion and the age, sex, or weight of the diabetic patients, nor was there any correlation between urinary chiro-inositol and myo-inositol excretion in either group. The results were similar in a primate model of NIDDM, and chiro-inositol excretion was decreased to a lesser extent in animals with prediabetic insulin resistance. chiro-Inositol was undetectable in insulin-mediator preparations from muscle-biopsy samples obtained from patients with NIDDM. Similar preparations from normal subjects contained substantial amounts of chiro-inositol. Furthermore, the chiro-inositol content of such preparations increased after the administration of insulin during euglycemic-hyperinsulinemic-clamp studies in normal subjects but not in patients with NIDDM. CONCLUSIONS. NIDDM is associated with decreased chiro-inositol excretion and decreased chiro-inositol content in muscle. These abnormalities seem to reflect the presence of insulin resistance in NIDDM.
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Department of Pharmacology, University of Virginia School of Medicine, Charlottesville.
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