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

L Brennan, A Shine, C Hewage, JPG Malthouse, KM Brindle, Neville McClenaghan, Peter Flatt, P Newsholme

Research output: Contribution to journalArticle

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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 C-13 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 -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.
LanguageEnglish
Pages1714-1721
JournalDiabetes
Volume51
Issue number6
Publication statusPublished - Jun 2002

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Insulin-Secreting Cells
Alanine
Magnetic Resonance Spectroscopy
Insulin
Glucose
Cell Line
Islets of Langerhans
Glutamic Acid
Oligomycins
Amino Acids
Citric Acid Cycle
Secretory Pathway
Oxidative Phosphorylation
Pyruvic Acid
Aspartic Acid
Rodentia
Lactic Acid
Adenosine Triphosphate

Cite this

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title = "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",
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 C-13 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 -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.",
author = "L Brennan and A Shine and C Hewage and JPG Malthouse and KM Brindle and Neville McClenaghan and Peter Flatt and P Newsholme",
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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. / Brennan, L; Shine, A; Hewage, C; Malthouse, JPG; Brindle, KM; McClenaghan, Neville; Flatt, Peter; Newsholme, P.

In: Diabetes, Vol. 51, No. 6, 06.2002, p. 1714-1721.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Brennan, L

AU - Shine, A

AU - Hewage, C

AU - Malthouse, JPG

AU - Brindle, KM

AU - McClenaghan, Neville

AU - Flatt, Peter

AU - Newsholme, P

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AB - 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 C-13 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 -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.

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