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After extending previous evidence that leptin infusion directly into the lateral cerebral ventricle ameliorates hyperglycemia in rats with streptozotocin-induced uncontrolled diabetes mellitus, we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic \u03b2-cells. Instead, leptin action in the brain potently suppresses hepatic glucose production while increasing tissue glucose uptake despite persistent, severe insulin deficiency. This leptin action is distinct from its previously reported effect to increase insulin sensitivity in the liver and offers compelling evidence that the brain has the capacity to normalize diabetic hyperglycemia in the presence of sufficient amounts of central nervous system leptin.<\/jats:p>","DOI":"10.1210\/en.2010-0890","type":"journal-article","created":{"date-parts":[[2010,12,16]],"date-time":"2010-12-16T04:04:34Z","timestamp":1292472274000},"page":"394-404","source":"Crossref","is-referenced-by-count":144,"title":["Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia"],"prefix":"10.1210","volume":"152","author":[{"given":"Jonathan P.","family":"German","sequence":"first","affiliation":[{"name":"Diabetes and Obesity Center of Excellence (J.P.G., J.P.T., B.E.W., S.O.-I., D.A.S., M.E.M., J.D.F., M.W.S., G.J.M.), Department of Medicine, University of Washington, Seattle, Washington 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