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Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
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Paradoxical insights into whole body metabolic adaptations following SGLT2 inhibition

William T Cefalu

    The Journal of Clinical Investigation
    |January 28, 2014
    PubMed

    Insights

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose in type 2 diabetes. Paradoxically, these drugs increase endogenous glucose production, impacting overall metabolism.

    Area of Science:

    • Endocrinology
    • Metabolic Diseases
    • Pharmacology

    Background:

    • Type 2 diabetes management focuses on glycemic control to prevent complications.
    • Hyperglycemia in type 2 diabetes worsens insulin resistance and beta cell function.
    • Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose by increasing urinary glucose excretion.

    Purpose of the Study:

    • To investigate the metabolic effects of SGLT2 inhibition in type 2 diabetes.
    • To understand the impact of SGLT2 inhibition on endogenous glucose production.

    Main Methods:

    • Clinical studies involving patients with type 2 diabetes treated with SGLT2 inhibitors.
    • Measurement of plasma glucose and endogenous glucose production.

    Main Results:

    • SGLT2 inhibition led to a paradoxical increase in endogenous glucose production.
    • Despite increased endogenous glucose production, fasting plasma glucose levels decreased overall.
    • These findings offer new insights into whole-body metabolism during SGLT2 inhibition.

    Conclusions:

    • SGLT2 inhibition has complex effects on glucose metabolism in type 2 diabetes.
    • Understanding the regulation of endogenous glucose production is crucial for SGLT2 inhibitor therapy.
    • Further research is needed to elucidate the mechanisms behind this metabolic adaptation.

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