Type

Journal Article

Authors

Philip Newsholme
Peter R Flatt
Neville McClenaghan
Kevin M Brindle
J.Paul G. Malthouse
Chandralal Hewage
Aine Shine
Lorraine Brennan

Subjects

Biochemistry

Topics
metabolism adenosine triphosphate oligomycins secretion glutamic acid pharmacology islets of langerhans pyruvic acid kinetics glucose insulin oxidative phosphorylation alanine drug effects carbon isotopes oxidation reduction cell line citric acid cycle clone cells lactic acid magnetic resonance spectroscopy

A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic beta-cell line: metabolism of L-alanine is important to the regulation of insulin secretion. (2002)

Abstract Early experiments indicated that islet beta-cells substantially metabolized L-alanine but that insulin secretion was largely unaffected by the amino acid. It was subsequently demonstrated using more intricate studies that L-alanine is a strong stimulus to insulin secretion in the presence of glucose in normal rodent islets and beta-cell lines. Using (13)C nuclear magnetic resonance (NMR), we have demonstrated substantial oxidative metabolism of L-alanine by the clonal beta-cell line BRIN-BD11, with time-dependent increases in production of cellular glutamate and aspartate. Stimulatory effects of L-alanine on insulin secretion were attenuated by the inhibition of beta-cell oxidative phosphorylation using oligomycin. Additionally, we detected substantial production of lactate, alanine, and glutamate from glucose (16.7 mmol/l) after 60 min. On addition of 10 mmol/l L-alanine to a stimulus of 16.7 mmol/l glucose, the utilization rate of glucose increased approximately 2.4-fold. L-Alanine dramatically enhanced NMR-measurable aspects of glucose metabolism (both oxidative and nonoxidative). The enhanced rate of entry of glucose-derived pyruvate into the tricarboxylic acid (TCA) cycle in the presence of alanine may have stimulated rates of generation of key metabolites, including ATP, which affect the insulin secretory process. Thus L-alanine metabolism, in addition to the enhancing effect on glucose metabolism, contributes to the stimulatory effects of this amino acid on insulin secretion in vitro.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Philip Newsholme, Peter R Flatt, Neville McClenaghan, Kevin M Brindle, J.Paul G. Malthouse, Chandralal Hewage, Aine Shine, Lorraine Brennan

Experts in our system

1
Philip Newsholme
University College Dublin
Total Publications: 51
 
2
J.Paul G. Malthouse
University College Dublin
Total Publications: 71
 
3
Lorraine Brennan
University College Dublin
Total Publications: 166