Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus

D. E. Kelley, L. J. Mandarino

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    149 Scopus citations


    The diminished ability of insulin to promote glucose disposal and storage in muscle has been ascribed to impaired activation of glycogen synthase (GS). It is possible that decreased glucose storage could occur as a consequence of decreased glucose uptake, and that GS is impaired secondarily. Muscle glucose uptake in 15 diabetic subjects was matched to 15 nondiabetic subjects by maintaining fasting hyperglycemia during infusion of insulin. Leg muscle glucose uptake, glucose oxidation (local indirect calorimetry), release of glycolytic products, and muscle glucose storage, as well as muscle GS and pyruvate dehydrogenase (PDH) were determined before and during insulin infusion. Basal leg glucose oxidation and PDH were increased in the diabetics. Insulin-stimulated leg glucose uptake in the diabetics (8.05 ± 1.41 μmol/[min·100 ml leg tissue]) did not differ from controls (5.64 ± 0.37). Insulin-stimulated leg glucose oxidation, nonoxidized glycolysis, and glucose storage (2.48 ± 0.27, 0.68 ± 0.15, and 5.04 ± 1.34 μmol/[min·100 ml], respectively) were not different from controls (2.18 ± 0.12, 0.62 ± 0.16, and 2.83 ± 0.31). PDH and GS in noninsulin-dependent diabetes mellitus (NIDDM) were also normal during insulin infusion. When diabetics were restudied after being rendered euglycemic by overnight insulin infusion, GS and PDH were reduced compared with hyperglycemia. Thus, fasting hyperglycemia is sufficient to normalize insulin-stimulated muscle glucose uptake in NIDDM, and glucose is distributed normally to glycogenesis and glucose oxidation, possibly by normalization of GS and PDH.

    Original languageEnglish (US)
    Pages (from-to)1999-2007
    Number of pages9
    JournalJournal of Clinical Investigation
    Issue number6
    StatePublished - 1990


    • glycogen synthase
    • muscle glucose metabolism
    • noninsulin-dependent diabetes mellitus
    • pyruvate dehydrogenase

    ASJC Scopus subject areas

    • Medicine(all)

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