Journal
WORLD JOURNAL OF DIABETES
Volume 5, Issue 5, Pages 666-677Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.4239/wjd.v5.i5.666
Keywords
Hyperinsulinaemic hypoglycaemia; KATP channel; Glutamate dehydrogenase; Hyperinsulinism/Hyperammonaemia; syndrome; Short-chain-3-hydroxyacylCoA-dehydrogenase; Glutamine
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Funding
- MRC [G1001821] Funding Source: UKRI
- Medical Research Council [G1001821] Funding Source: Medline
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The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors (such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase (GDH) and HADH gene, en-coding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
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