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Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
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Hypothalamic resistin induces hepatic insulin resistance.
Evan D Muse1, Tony K T Lam, Philipp E Scherer
1Department of Molecular Pharmacology, Albert Einstein College of Medicine of Yeshiva University, New York, NY 10461, USA.
The Journal of Clinical Investigation
|May 26, 2007
Summary
Hypothalamic resistin action significantly impacts glucose production and liver inflammation. Targeting this pathway may offer new strategies for managing hyperglycemia in type 2 diabetes mellitus.
Area of Science:
- Endocrinology
- Neuroscience
- Metabolic Research
Background:
- Resistin, a hormone, is known to stimulate endogenous glucose production (GP).
- The precise mechanisms and central regulation of resistin's effects on glucose metabolism and inflammation are not fully understood.
Purpose of the Study:
- To investigate the role of hypothalamic resistin action on glucose production.
- To explore the influence of central resistin signaling on hepatic proinflammatory cytokine expression.
- To determine if central mechanisms mediate resistin's effects on GP and inflammation.
Main Methods:
- Infusion of resistin or a cysteine mutant into the third cerebral ventricle (icv) or mediobasal hypothalamus.
- Central antagonism of resistin action.
- Measurement of glucose production (GP) and hepatic expression of TNF-alpha, IL-6, and SOCS-3.
Main Results:
- Central resistin administration stimulated GP independently of systemic hormones.
- Central antagonism of resistin action reduced the effect of circulating resistin on GP.
- Centrally mediated pathways partially regulate resistin-induced hepatic expression of TNF-alpha, IL-6, and SOCS-3.
Conclusions:
- The hypothalamus represents a novel site of action for resistin influencing glucose production.
- Central resistin signaling plays a role in regulating hepatic inflammation.
- Hypothalamic resistin action may contribute to hyperglycemia in type 2 diabetes mellitus.
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