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Mechanisms of Hypothalamic and Small Intestinal Nutrient Sensing

Nutrient sensing pathways in both the brain and gut decrease hepatic glucose production. Hypothalamic activation of lactate metabolism decreases glucose production, but it is unknown whether the hypothalamus detects circulating lactate to maintain glucose homeostasis. In the gut, lipids decrease glucose production via a neuronal network but the downstream signaling mechanisms are unknown. We tested whether circulating lactate activates central lactate metabolism to decrease glucose production and postulated that duodenal protein kinase C (PKC) acts downstream of lipids to decrease glucose production through a neuronal network. We report that central lactate metabolism is required for the maintenance of glucose homeostasis in the presence of circulating lactate and that activation of duodenal PKC is required for lipids to decrease glucose production. This shows the importance of the brain and gut in the regulation of glucose production, and could pave the way for restoration of glucose homeostasis in disease.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/26525
Date22 March 2011
CreatorsKokorovic, Andrea
ContributorsLam, Tony K. T.
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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