کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2793678 1155170 2007 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mitochondrial GTP Regulates Glucose-Stimulated Insulin Secretion
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Mitochondrial GTP Regulates Glucose-Stimulated Insulin Secretion
چکیده انگلیسی

SummaryNucleotide-specific isoforms of the tricarboxylic acid (TCA) cycle enzyme succinyl-CoA synthetase (SCS) catalyze substrate-level synthesis of mitochondrial GTP (mtGTP) and ATP (mtATP). While mtATP yield from glucose metabolism is coupled with oxidative phosphorylation and can vary, each molecule of glucose metabolized within pancreatic β cells produces approximately one mtGTP, making mtGTP a potentially important fuel signal. In INS-1 832/13 cells and cultured rat islets, siRNA suppression of the GTP-producing pathway (ΔSCS-GTP) reduced glucose-stimulated insulin secretion (GSIS) by 50%, while suppression of the ATP-producing isoform (ΔSCS-ATP) increased GSIS 2-fold. Insulin secretion correlated with increases in cytosolic calcium, but not with changes in NAD(P)H or the ATP/ADP ratio. These data suggest a role for mtGTP in controlling pancreatic GSIS through modulation of mitochondrial metabolism, possibly involving mitochondrial calcium. Furthermore, in light of its tight coupling to TCA oxidation rates, mtGTP production may serve as an important molecular signal of TCA-cycle activity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 5, Issue 4, 4 April 2007, Pages 253–264
نویسندگان
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