Metabolic consequence of long-term exposure of pancreatic β cells to free fatty acid with special reference to glucose insensitivity

Katsumi Iizuka, Hiromu Nakajima, Mitsuyoshi Namba, Jun ichiro Miyagawa, Junichi Miyazaki, Toshiaki Hanafusa, Yuji Matsuzawa

研究成果: Article査読

31 被引用数 (Scopus)

抄録

Long-term exposure of the pancreatic β cells to free fatty acid (FFA) reportedly inhibits glucose-stimulated insulin secretion. We here studied the impact of FFA on glucose and lipid metabolism in pancreatic β cells with special reference to insulin secretion. Pancreatic β-cell line MIN6 was exposed to various concentrations of palmitate for 3 days. Glucose-stimulated insulin secretion and insulin content were decreased corresponding to the concentration of the palmitate exposed. Glycolytic flux and ATP synthesis was unchanged, but pyruvate-stimulated change in NAD(P)H concentration was decreased. Pyruvate carboxylase was decreased at the protein level, which was restored by the removal of palmitate or the inhibition of β-oxidation. Intracellular content of triglyceride and FFA were elevated, β-oxidation was increased, and de novo lipogenesis from glucose was decreased. NADPH content and citrate output into the medium, which reflected pyruvate malate shuttle flux, were decreased, but malic enzyme activity was unaffected. The malic enzyme inhibitor alone inhibited insulin response to glucose. In conclusion, long-term exposure of FFA to β cells inhibits glucose-stimulated insulin secretion via the decreased NADPH contents due to the inhibition of pyruvate carboxylase and malate pyruvate shuttle flux.

本文言語English
ページ(範囲)23-31
ページ数9
ジャーナルBiochimica et Biophysica Acta - Molecular Basis of Disease
1586
1
DOI
出版ステータスPublished - 02-01-2002
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 分子生物学

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