title: Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition.
abstract: Leucine has been shown to acutely inhibit hepatic glucose production in rodents by a mechanism requiring its metabolism to acetyl-CoA in the mediobasal hypothalamus (MBH). In the early stages, all branched-chain amino acids (BCAA) are metabolized by a shared set of enzymes to produce a ketoacid, which is later metabolized to acetyl-CoA. Consequently, isoleucine and valine may also modulate glucose metabolism. To examine this possibility we performed intrahypothalamic infusions of isoleucine or valine in rats and assessed whole body glucose kinetics under basal conditions and during euglycemic pancreatic clamps. Furthermore, because high fat diet (HFD) consumption is known to interfere with central glucoregulation, we also asked whether the action of BCAAs was affected by HFD. We fed rats a lard-rich diet for a short interval and examined their response to central leucine. The results showed that both isoleucine and valine individually lowered blood glucose by decreasing liver glucose production. Furthermore, the action of the BCAA leucine was markedly attenuated by HFD feeding. We conclude that all three BCAAs centrally modulate glucose metabolism in the liver and that their action is disrupted by HFD-induced insulin resistance.
authors.affiliation: National Institute of Geriatrics, Ministry of Health, Periférico Sur No. 2767, Col. San Jerónimo Lídice. Del. Magdalena Contreras, Mexico City 10200, Mexico. arrieta777@mail.com.
authors.forename: Isabel
authors.initials: I
authors.lastname: Arrieta-Cruz
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Ave, Bronx, NY 10461, USA. ya.su@einstein.yu.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Ave, Bronx, NY 10461, USA. roger.gutierrez@einstein.yu.edu.
authors.forename: Roger
authors.initials: R
authors.lastname: Gutiérrez-Juárez
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004032:Diet; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D004044:Dietary Proteins / Q000737:chemistry* / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism; D007333:Insulin Resistance; D007532:Isoleucine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley; D014633:Valine / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D004044:Dietary Proteins; D007532:Isoleucine; D014633:Valine; C029310:lard
keywords: branched-chain amino acids; glucose metabolism; hypothalamus; isoleucine; leucine; liver; nutrient sensing; valine