کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3001527 1180647 2016 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion
ترجمه فارسی عنوان
نقش اجدادی برای حامل پیوسته میتوکندری در ترشح انسولین تحریک گلوکز
کلمات کلیدی
ترشح محرک جنین؛ انسولین؛ β-Cell؛ دیابت؛ پیروات؛ میتوکندریا؛ DrosophilaIMM، غشای میتوکندری درونی؛ MPC1 و MPC2، حامل 1 و 2 پیوروتوم میتوکندری؛ GSIS، ترشح انسولین تحریک شده توسط گلوکز؛ IPCs، سلول های تولید کننده انسولین؛ O
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی سیستم های درون ریز و اتونومیک
چکیده انگلیسی


• Loss of MPC activity in Drosophila leads to hyperglycemia.
• Glucose-stimulated insulin secretion is impaired in Drosophila lacking MPC.
• β-cell-specific MPC deletion in mice also results in impaired insulin secretion.
• The MPC may be a sensor for glucose concentration in β-cells and couple pyruvate production to insulin secretion.

ObjectiveTransport of pyruvate into the mitochondrial matrix by the Mitochondrial Pyruvate Carrier (MPC) is an important and rate-limiting step in its metabolism. In pancreatic β-cells, mitochondrial pyruvate metabolism is thought to be important for glucose sensing and glucose-stimulated insulin secretion.MethodsTo evaluate the role that the MPC plays in maintaining systemic glucose homeostasis, we used genetically-engineered Drosophila and mice with loss of MPC activity in insulin-producing cells.ResultsIn both species, MPC deficiency results in elevated blood sugar concentrations and glucose intolerance accompanied by impaired glucose-stimulated insulin secretion. In mouse islets, β-cell MPC-deficiency resulted in decreased respiration with glucose, ATP-sensitive potassium (KATP) channel hyperactivity, and impaired insulin release. Moreover, treatment of pancreas-specific MPC knockout mice with glibenclamide, a sulfonylurea KATP channel inhibitor, improved defects in islet insulin secretion and abnormalities in glucose homeostasis in vivo. Finally, using a recently-developed biosensor for MPC activity, we show that the MPC is rapidly stimulated by glucose treatment in INS-1 insulinoma cells suggesting that glucose sensing is coupled to mitochondrial pyruvate carrier activity.ConclusionsAltogether, these studies suggest that the MPC plays an important and ancestral role in insulin-secreting cells in mediating glucose sensing, regulating insulin secretion, and controlling systemic glycemia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Metabolism - Volume 5, Issue 8, August 2016, Pages 602–614
نویسندگان
, , , , , , , ,