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Hypothalamic sensing of circulating lactate regulates glucose production
Andrea Kokorovic1, Grace W C Cheung, Luciano Rossetti
1Department of Physiology, University of Toronto, Toronto, Canada.
Journal of Cellular and Molecular Medicine
|December 2, 2008
Summary
The hypothalamus senses circulating lactate to regulate glucose production and maintain homeostasis. Inhibiting this sensing mechanism increases glucose production, highlighting its critical role in glucose metabolism.
Area of Science:
- Neuroendocrinology
- Metabolic Regulation
- Glucose Homeostasis
Background:
- Hypothalamic hormonal pathways and nutrient metabolism are known regulators of glucose homeostasis.
- While central lactate sensing lowers glucose production, its role in sensing circulating lactate in vivo remains unclear.
Purpose of the Study:
- To investigate if hypothalamic sensing of circulating lactate is essential for regulating glucose production (GP) and maintaining glucose homeostasis in vivo.
Main Methods:
- Intravenous (i.v.) lactate infusion in rodents with and without inhibition of central/hypothalamic lactate sensing.
- Three independent methods were used to inhibit lactate sensing.
- Tracer-dilution and pancreatic clamp techniques assessed glucose metabolism.
Main Results:
- Inhibition of central lactate sensing increased GP during elevated plasma lactate levels.
- Lactate dehydrogenase inhibitor oxamate (OXA) and glibenclamide increased GP.
- Direct hypothalamic OXA administration also increased GP.
Conclusions:
- Hypothalamic sensing of circulating lactate plays a crucial role in regulating glucose production.
- This sensing mechanism is vital for maintaining glucose homeostasis in vivo.
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