Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic -cells

نویسندگان

  • Kazuhiro Eto
  • Tokuyuki Yamashita
  • Kenzo Hirose
  • Yoshiharu Tsubamoto
  • Edward K. Ainscow
  • Guy A. Rutter
  • Satoshi Kimura
  • Mitsuhiko Noda
  • Masamitsu Iino
  • Takashi Kadowaki
چکیده

Kazuhiro Eto,1,3 Tokuyuki Yamashita,1 Kenzo Hirose,2 Yoshiharu Tsubamoto,1 Edward K. Ainscow,5 Guy A. Rutter,5 Satoshi Kimura,1 Mitsuhiko Noda,3,4 Masamitsu Iino,2 and Takashi Kadowaki1,3 Departments of 1Metabolic Diseases and 2Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655; 3CREST of Japan Science and Technology Corporation, Saitama 332-0012; 4Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo 100-0005, Japan; and 5Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic beta-cells.

We studied acute changes of secretory vesicle pH in pancreatic beta-cells with a fluorescent pH indicator, lysosensor green DND-189. Fluorescence was decreased by 0.66 +/- 0.10% at 149 +/- 16 s with 22.2 mM glucose stimulation, indicating that vesicular pH was alkalinized by approximately 0.016 unit. Glucose-responsive pH increase was observed when cytosolic Ca2+ influx was blocked but disappea...

متن کامل

Essential roles of aspartate aminotransferase 1 and vesicular glutamate transporters in β-cell glutamate signaling for incretin-induced insulin secretion

Incretins (GLP-1 and GIP) potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS) that requires two critical processes: 1) generation of cytosolic glutamate through the malate-aspartate (MA) shuttle in glucose metabolism and 2) glutamate transport into insulin g...

متن کامل

Increase in cellular glutamate levels stimulates exocytosis in pancreatic beta-cells.

Glutamate has been implicated as an intracellular messenger in the regulation of insulin secretion in response to glucose. Here we demonstrate by measurements of cell capacitance in rat pancreatic beta-cells that glutamate (1 mM) enhanced Ca2+-dependent exocytosis. Glutamate (1 mM) also stimulated insulin secretion from permeabilized rat beta-cells. The effect was dose-dependent (half-maximum a...

متن کامل

5'-AMP-activated protein kinase controls insulin-containing secretory vesicle dynamics.

Changes in 5'-AMP-activated protein kinase (AMPK) activity have recently been implicated in the control of insulin secretion by glucose (da Silva Xavier, G., Leclerc, I., Varadi, A., Tsuboi, T., Moule, S. K., and Rutter, G. A. (2003) Biochem. J. 371, 761-774). Here, we examine the possibility that activation of AMPK may regulate distal steps in insulin secretion, including vesicle movement and ...

متن کامل

GAD65-mediated glutamate decarboxylation reduces glucose-stimulated insulin secretion in pancreatic beta cells.

Mitochondrial metabolism plays a pivotal role in the pancreatic beta cell by generating signals that couple glucose sensing to insulin secretion. We have demonstrated previously that mitochondrially derived glutamate participates directly in the stimulation of insulin exocytosis. The aim of the present study was to impose altered cellular glutamate levels by overexpression of glutamate decarbox...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2003