Review
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World J Diabetes. Oct 15, 2014; 5(5): 666-677
Published online Oct 15, 2014. doi: 10.4239/wjd.v5.i5.666
Molecular mechanisms of protein induced hyperinsulinaemic hypoglycaemia
Suresh Chandran, Fabian Yap, Khalid Hussain
Suresh Chandran, Department of Neonatology, KK Women’s and Children’s Hospital, Singapore 229899, Singapore
Suresh Chandran, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117598, Singapore
Fabian Yap, Department of Paediatric Endocrinology, KK Women’s and Children’s Hospital, Singapore 229899, Singapore
Suresh Chandran, Fabian Yap, Duke-NUS Graduate Medical School, Singapore 169857, Singapore
Suresh Chandran, Fabian Yap, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
Khalid Hussain, Departments of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom
Khalid Hussain, Developmental Endocrinology Research Group, Molecular Genetics Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom
Author contributions: Chandran S and Yap F wrote the review under the supervision of Hussain K; Hussain K contributed to abstract, introduction written and final editing of the manuscript.
Correspondence to: Dr. Khalid Hussain, Reader/Honorary Consultant Paediatric Endocrinologist, Developmental Endocrinology Research Group, Molecular Genetics Unit, Institute of Child Health, University College London, 30 Guildford Street, London WC1N 1EH, United Kingdom. khalid.hussain@ucl.ac.uk
Telephone: +44-20-79052128 Fax: +44-20-74046191
Received: January 21, 2014
Revised: April 29, 2014
Accepted: May 28, 2014
Published online: October 15, 2014
Processing time: 207 Days and 15.4 Hours
Core Tip

Core tip: The interplay between glucose, amino acid and fatty acid metabolism 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 [encoding for the enzyme glutamate dehydrogenase (GDH)] and HADH genes, has provided novel 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.