Year: 2013
Type: article
Abstract: Insulin-independent glucose disposal (referred to as glucose effectiveness [GE]) is crucial for glucose homeostasis and, until recently, was thought to be invariable. However, GE is reduced in type 2 diabetes and markedly decreased in leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore be capable of improving glucose tolerance in these animals. The gut-derived hormone FGF19 has previously been shown to exert potent antidiabetic effects in ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved glucose tolerance through its action in the brain and that a single, low-dose i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2 hours. Minimal model analysis of glucose and insulin data obtained during a frequently sampled i.v. glucose tolerance test showed that the antidiabetic effect of i.c.v. FGF19 was solely due to increased GE and not to changes of either insulin secretion or insulin sensitivity. The mechanism underlying this effect appears to involve increased metabolism of glucose to lactate. Together, these findings implicate the brain in the antidiabetic action of systemic FGF19 and establish the brain’s capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal.
DOI: 10.1172/jci70710
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1153718808, G1221739687, G1228426491, Neurocircuits that regulate circadian rhythms, G1948980911, G234089594, Vanderbilt Mouse Metabolic Phenotyping Center, G4424950377, G5617877370, CNS Mechanisms Controlling Blood Glucose Levels in Uncontrolled Diabetes Mellitus, Quantitation of Factors Regulating Glucose Tolerance, G698671413, G7388217856, Hypothalamic Inflammation and Energy Homeostasis, G9000024636, G9000132431, G9000146489, Nutrition Obesity Research Center, Diabetes Research Center, Divergent Mechanisms Underlying Anorexic and Antidiabetic Actions of FGF1 in the Brain, Diabetes, Obesity and Metabolism Training Program
OpenAlex ID: W2038122889