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Related Experiment Video

Updated: May 6, 2026

Combined Intravital Microscopy and Contrast-enhanced Ultrasonography of the Mouse Hindlimb to Study Insulin-induced Vasodilation and Muscle Perfusion
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Insulin resistance in uremia

R A DeFronzo, A Alvestrand, D Smith

    The Journal of Clinical Investigation
    |February 1, 1981
    PubMed
    Summary

    Chronic kidney disease (CKD) causes insulin resistance, primarily due to impaired glucose uptake in peripheral tissues, not liver dysfunction. This study highlights the critical role of peripheral tissues in CKD-related insulin resistance.

    Area of Science:

    • Endocrinology
    • Metabolism
    • Nephrology

    Background:

    • Chronic kidney disease (CKD) is associated with insulin resistance.
    • The specific mechanisms underlying insulin resistance in CKD are not fully understood.
    • Investigating tissue-specific insulin sensitivity is crucial for understanding metabolic derangements in CKD.

    Purpose of the Study:

    • To determine tissue-specific insulin sensitivity in chronically uremic subjects.
    • To differentiate between hepatic and peripheral tissue contributions to insulin resistance in uremia.
    • To elucidate the primary cause of insulin resistance in chronic kidney disease.

    Main Methods:

    • Utilized the euglycemic insulin clamp technique to assess whole-body insulin sensitivity.
    • Measured basal and insulin-suppressed hepatic glucose production using [3H]-3-glucose.

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  • Employed hepatic venous catheterization to directly measure splanchnic glucose balance.
  • Quantified glucose uptake in peripheral tissues, specifically the leg.

    • Main Results:

    • Uremic subjects exhibited a 47% reduction in insulin-mediated glucose metabolism compared to controls.
    • Hepatic glucose production was normal in uremia and suppressed appropriately by insulin.
    • Insulin-mediated glucose uptake by the liver was normal in uremic individuals.
    • Glucose uptake by leg tissues was significantly reduced (60%) in uremic subjects.

    Conclusions:

    • Insulin resistance in chronic kidney disease is primarily due to impaired peripheral tissue glucose uptake.
    • Hepatic glucose production and insulin-mediated hepatic glucose uptake are not impaired in uremia.
    • Peripheral tissue insensitivity to insulin is the main driver of insulin resistance in CKD.