title: Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation.
abstract: We herein studied the role of glutamate dehydrogenase (GDH), in response to leucine (LEU) supplementation, upon insulin secretion of malnourished rats. Weaned male Wistar rats were fed normal-protein (17%) or low-protein diet (6%, LP) for 8 weeks. Half of the rats of each group were supplemented with LEU (1.5%) in the drinking water for the following 4 weeks. Gene and protein expressions, static insulin secretion, and cytoplasmic Ca(2+) oscillations were measured. Glutamate dehydrogenase messenger RNA was 58% lower in LP islets, and LEU supplementation augmented it in 28%. The LP islets secreted less insulin when exposed to 20 mmol/L LEU, 20 mmol/L LEU + 2 mmol/L glutamine (with or without 5 mmol/L aminooxyacetic acid, a branched chain aminotransferase inhibitor, or 20 μmol/L epigallocatechin gallate, a GDH inhibitor), 20 mmol/L α-ketoisocaproate, glutamine + 20 mmol/L β-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (a GDH activator), and 22.2 mmol/L glucose. Leucine supplementation augmented insulin secretion to levels found in normal-protein islets in all the above conditions, an effect that was blunted when islets were incubated with epigallocatechin gallate. The glutamine + β-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid-induced increased [Ca(2+)](i) and oscillations were higher than those for LP islets. Leucine supplementation normalized these parameters in LP islets. Impaired GDH function was associated with lower insulin release in LP islets, and LEU supplementation normalized insulin secretion via restoration of GDH function. In addition, GDH may contribute to insulin secretion through ameliorations of Ca(2+) handling in LP islets.
authors.affiliation: Department of Anatomy, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas,PO Box 6109, CEP 13083-970 Campinas, SP, Brazil.
authors.forename: Priscilla Muniz Ribeiro
authors.initials: PM
authors.lastname: da Silva
authors.forename: Thiago Martins
authors.initials: TM
authors.lastname: Batista
authors.forename: Rosane Aparecida
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Claudio Cesar
authors.initials: CC
authors.lastname: Zoppi
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Boschero
authors.forename: Everardo Magalhães
authors.initials: EM
authors.lastname: Carneiro
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D004032:Diet; D019587:Dietary Supplements; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005969:Glutamate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000502:physiology; D011502:Protein-Energy Malnutrition / Q000201:enzymology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D005969:Glutamate Dehydrogenase; D007930:Leucine; D002118:Calcium