Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia

Rory J. McCrimmon (Lead / Corresponding author), Margaret Shaw, Xiaoning Fan, Haiying Cheng, Yuyan Ding, Monica C. Vella, Ligang Zhou, Ewan C. Mcnay, Robert S. Sherwin

    Research output: Contribution to journalArticlepeer-review

    111 Citations (Scopus)

    Abstract

    OBJECTIVE-To examine in vivo in a rodent model the potential role of AMP-activated protein kinase (AMPK) within the ventromedial hypothalamus (VMH) in glucose sensing during hypoglycemia.

    RESEARCH DESIGN AND METHODS-Using gene silencing technology to selectively downregulate AMPK in the VMH, a key hypothalamic glucose-sensing region, we demonstrate a key role for AMPK in the detection of hypoglycemia. In vivo hyperinsulinemic-hypoglycemic (50 mg dl(-1)) clamp studies were performed in awake, chronically catheterized Sprague-Dawley rats that had been microinjected bilaterally to the VMH with an adeno-associated viral (AAV) vector expressing a short hairpin RNA for AMPK alpha.

    RESULTS-In comparison with control studies, VMH AMPK downregulation resulted in suppressed glucagon (similar to 60%) and epinephrine (similar to 40%) responses to acute hypoglycemia. Rats with VMH AMPK downregulation also required more exogenous glucose to maintain the hypoglycemia plateau and showed significant reductions in endogenous glucose production and whole-body glucose uptake.

    CONCLUSIONS-We conclude that AMPK in the VMH plays a key role in the detection of acute hypoglycemia and initiation of the glucose counterregulatory response.

    Original languageEnglish
    Pages (from-to)444-450
    Number of pages7
    JournalDiabetes
    Volume57
    Issue number2
    DOIs
    Publication statusPublished - Feb 2008

    Keywords

    • DIFFERING INSULIN LEVELS
    • CENTRAL-NERVOUS-SYSTEM
    • SENSITIVE K+ CHANNELS
    • FOOD-INTAKE
    • EQUIVALENT HYPOGLYCEMIA
    • PORTAL-VEIN
    • SYMPATHOADRENAL RESPONSE
    • PROJECTION NEURONS
    • ACCUMBENS NUCLEUS
    • AUTONOMIC FAILURE

    Cite this