Fasting hyperglycemia normalizes oxidative and nonoxidative pathways of insulin-stimulated glucose metabolism in noninsulin-dependent diabetes mellitus

Lawrence J. Mandarino, Agostino Consoli, David E. Kelley, James J. Reilly, Nurjahan Nurjhan

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    Abstract

    The present studies were undertaken to determine whether fasting hyperglycemia can compensate for decreased insulin-stimulated glucose disposal, oxidation, and storage in noninsulin-dependent diabetes mellitus (NIDDM) as well as to determine whether hyperglycemia normalizes insulin-stimulated skeletal muscle glycogen synthase and pyruvate dehydrogenase (PDH) activities. To accomplish this, we used the glucose clamp technique with isotopic determination of glucose disposal and indirect calorimetry for measuring the pathways of glucose metabolism, and vastus lateralis muscle biopsies to determine the effects of insulin on glycogen synthase and PDH activities. Nine patients with NIDDM and eight matched nondiabetic subjects were infused with insulin (40 mU/m2·min) while plasma glucose was maintained at the prevailing fasting concentration. During insulin infusion, rates of glucose disposal, storage, and oxidation were the same in the two groups. Insulin infusion significantly activated glycogen synthase fractional velocity to the same extent in NIDDM (0.210 ± 0.056 vs. 0.332 ± 0.079) and controls (0.192 ± 0.036 us. 0.294 ± 0.050). Insulin infusion increased PDH fractional velocity in controls (from 0.281 ± 0.022 to 0.404 ± 0.038), but not in NIDDM (from 0.356 ± 0.043 to 0.436 ± 0.060), although the activity of PDH during insulin infusion did not differ between the groups. We conclude that prevailing fasting hyperglycemia normalizes the nonoxidative and oxidative pathways of insulin-stimulated glucose in metabolism in NIDDM and may act as a homeostatic mechanism to normalize muscle glucose metabolism.

    Original languageEnglish (US)
    Pages (from-to)1544-1551
    Number of pages8
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume71
    Issue number6
    DOIs
    StatePublished - Dec 1990

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    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Biochemistry
    • Endocrinology
    • Clinical Biochemistry
    • Biochemistry, medical

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