Pathogenesis of A(-)beta(+) Ketosis-Prone Diabetes

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	Pathogenesis of A(-)beta(+) Ketosis-Prone Diabetes
	Patel, S. G.
刊名	Diabetes
	2013
卷号	62 期号:3 页码:912-922
ISSN号	0012-1797
中文摘要	A(-)beta(+) ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible beta-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnitines, and amino acids were quantified in 20 KPD patients compared with 19 nondiabetic control subjects. Unique signatures in KPD-higher glutamate but lower glutamine and citrulline concentrations, increased beta-hydroxybutyryl-carnitine, decreased isovaleryl-carnitine (a leucine catabolite), and decreased tricarboxylic acid (TCA) cycle intermediates-generated hypotheses that were tested through stable isotope/mass spectrometry protocols in nine new-onset, stable KPD patients compared with seven nondiabetic control subjects. Free fatty acid flux and acetyl CoA flux and oxidation were similar, but KPD had slower acetyl CoA conversion to beta-hydroxybutyrate; higher fasting beta-hydroxybutyrate concentration; slower beta-hydroxybutyrate oxidation; faster leucine oxidative decarboxylation; accelerated glutamine conversion to glutamate without increase in glutamate carbon oxidation; and slower citrulline flux, with diminished glutamine amide-nitrogen transfer to citrulline. The confluence of metabolomic and kinetic data indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty acid utilization for energy, leading to accelerated leucine catabolism and transamination of alpha-ketoglutarate to glutamate, with impaired TCA anaplerosis of glutamate carbon. They highlight a novel process of defective energy production and ketosis in A(-)beta(+) KPD. Diabetes 62:912-922, 2013
公开日期	2015-03-27
内容类型	期刊论文
源URL	[http://ir.xtbg.org.cn/handle/353005/8494]
专题	西双版纳热带植物园_公共技术服务中心主要仪器相关文献_同位素质谱仪
推荐引用方式 GB/T 7714	Patel, S. G.. Pathogenesis of A(-)beta(+) Ketosis-Prone Diabetes[J]. Diabetes,2013,62(3):912-922.
APA	Patel, S. G..(2013).Pathogenesis of A(-)beta(+) Ketosis-Prone Diabetes.Diabetes,62(3),912-922.
MLA	Patel, S. G.."Pathogenesis of A(-)beta(+) Ketosis-Prone Diabetes".Diabetes 62.3(2013):912-922.