Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of insulin secretion from a mouse pancreatic beta-cell line

K. Iizuka, H. Nakajima, A. Ono, K. Okita, J. I. Miyazaki, J. I. Miyagawa, M. Namba, T. Hanafusa, Y. Matsuzawa

研究成果: Article査読

16 被引用数 (Scopus)

抄録

Glucose-6-phosphatase (G-6-Pase) hydrolyzes glucose-6-phosphate to glucose, reciprocal with the so-called glucose sensor, glucokinase, in pancreatic beta cells. To study the role of G-6-Pase in glucose-stimulated insulin secretion from beta cells, we have introduced rat G-6-Pase catalytic subunit cDNA and have established permanent clones with 3-, 7- and 24-fold G- 6-Pase activity of the mouse beta-cell line, MIN6. In these clones, glucose usage and ATP production in the presence of 5.5 or 25 mM glucose were reduced, and glucose-stimulated insulin secretion was decreased in proportion to the increased G-6-Pase activity. In addition, insulin secretory capacity in response to D-fructose and pyruvate was unchanged; however, 25 mM glucose- stimulated insulin secretion and intracellular calcium response were completely inhibited. In the clone with 24-fold G-6-Pase activity, changes in intracellular NAD(P)H autofluorescence in response to 25 mM glucose were reduced, but the changes with 20 mM fructose and 20 mM pyruvate were not altered. Stable overexpression of G-6-Pase in beta cells resulted in attenuation of the overall glucose-stimulated metabolic responses corresponding to the degree of overexpression. This particular experimental manipulation shows that the possibility exists of modulating glucose- stimulated insulin release by thoroughly altering glucose cycling at the glucokinase/G-6-Pase step.

本文言語English
ページ(範囲)307-314
ページ数8
ジャーナルJournal of Endocrinology
164
3
DOI
出版ステータスPublished - 2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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