Mitochondria‐derived glutamate at the interplay between branched‐chain amino acid and glucose‐induced insulin secretion

FEBS Letters

Broca, Christophe²  Petit, Pierre¹  Newsholme, Philip³  Brennan, Lorraine³  Maechler, Pierre² 

[1] CNRS UMR-5094 and UPRES EA-1677, Department of Pharmacology, Institute of Biology, Boulevard Henri 4, 34060 Montpellier, France;DBC-9100, Department of Internal Medicine, University Medical Centre, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland;Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland

关键词: Insulin secretion;    Glutamate dehydrogenase;    Glutamine;    Mitochondrion;    Nuclear magnetic resonance;    BCH;    2-aminobicyclo-[2;    2;    1]heptane-2-carboxylic acid;    GDH;    glutamate dehydrogenase;    NMR;    nuclear magnetic resonance;    KRB;    Krebs–Ringer bicarbonate buffer;    PBS;    phosphate-buffered saline;   

DOI  :  10.1016/S0014-5793(03)00526-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In pancreatic β-cells, glutamate has been proposed to mediate insulin secretion as a glucose-derived factor, although it is also considered for its sole catabolic function. Hence, changes in cellular glutamate levels are a matter of debate. Here, we investigated the effects of glucose and the glutamate precursor glutamine on kinetics of glutamate levels together with insulin secretion in INS-1E β-cells. Preincubation at low (1 mM) glucose resulted in reduced cellular glutamate levels, which were doubled by exposure to glutamine. In glutamine-deprived cells, 5 mM glucose restored glutamate concentrations. Incubation at 15 mM glucose increased cellular glutamate, along with stimulation of insulin secretion, following both glutamine-free and glutamine-rich preincubations. Nuclear magnetic resonance (NMR) spectroscopy of INS-1E cells exposed to 15 mM D-[1-¹³C]glucose revealed glutamate as the major glucose metabolic product. Branched-chain amino acids, such as leucine, reduced cellular glutamate levels at low and intermediate glucose. This study demonstrates that glucose stimulates glutamate generation, whereas branched-chain amino acids promote competitive glutamate expenditure.

【 授权许可】

Unknown