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2002 Fiscal Year Final Research Report Summary

Molecular physiological and biological studies on the effect of free fatty acids on pancreatic β cell function

Research Project

Project/Area Number 12671126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKyorin University

Principal Investigator

ISHIDA Hitoshi  Professor, Third Department of Internal Medicine, Kyorin University, 医学部, 教授 (80212893)

Co-Investigator(Kenkyū-buntansha) NAGAMATSU Shinya  Professor, Second Department of Biochemistry, Kyorin University, 医学部, 教授 (80231489)
Project Period (FY) 2000 – 2002
Keywordsproinsulin / free fatty acids / insulin secretion / intracellular calcium / PPARγ / glucagon secretion / exocytotic system / insulin biosynthesis
Research Abstract

In order to determine whether free fatty acids affect pancreatic βcell functions, the effect of palmitic acid on proinsulin biosynthesis and insulin secretion was studied using isolated rat islets. Expose of islets to palmitic acid for 1 hour reduced glucose-stimulated insulin biosynthesis, whereas no change in insulin secretion was observed. Thus, palmitic acid primarily suppress glucose-induced proinsulin prior to alteration of insulin release. It has been known that long expose of free fatty acids leads the overexpression of peroxisome proliferator-activated receptor γ (PPAR γ) in pancreatic islets. Then, the effect of PPAR γ overepression on the secretion of insulin and glucagon was investigated in vitro. The glucose-stimulated and high potassium-induced insulin secretion was markedly reduced through PPAR γ overexpression. However, the glucagon release by high-potassium depolarization was not changed. The deteriorative effect seems to be, therefore, β-cell specific. Recently, many research groups have tried to expand or regenerate pancreatic β cells by genetic engineering techniques, however, a definite way to regulate insulin secretion was not established. We took advance to facts that adopocytes characteristically secrete many cytokines such as TNF-α and adiponectin, and that the regulated exocytotic pathway to GLUT4 can be triggered by insulin stimulation. Interestingly, when adenovirus-mediated preproinsulin gene was transferred into 3T31_l adipocytes, expressed proinsulin was co-localized with GLUT4 vesicle and was found to be processed into insulin. The gene transfer into adipose tissues ameliorates hyperglycemia in obese diabetic KKAy mice for at least 2 weeks. The subsequent elimination of glucose toxicity can be expected to restore pancreatic β cell function in diabetes.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Y.Nakamichi, H.Ishida, et al.: "An insulin-related peptide expressed in 3T3L1 adipocytes is loclized in GLUT4 vesicles and secreted in response to exogenous insulin, which augments the insulin-stimulated glucose uptake"J Cell Sci. 116. 73-79 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Kimoto, H.Ishida, et al.: "Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide"Biochem Biophys Res Commun. 303. 112-119 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Ohara-Imaizumi, H.Ishida, et al.: "Monitoring of exocytosis and endocytosis of insulin secretory granules in the pancreatic β-cell line MIN6 using pH-sensitive green fluorescent protein"Biochem J. 363. 73-80 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Ohara-Imaizumi, H.Ishida, et al.: "Imaging exocytosis of single insulin secretory granules with evanescent wave microscopy -Distinct behavior of granule motion in biphasic insulin release-"J Biol Chem. 277・6. 3805-3808 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Katahira, H.Ishida, et al.: "Acute inhibition of proinsulin biosynthesis at the translational level by palmitic acid"Biochem Biophys Res Commun. 282. 507-510 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Nagamatsu, H.Ishida, et al.: "Localization of cellubrevin-related peptide, endobrevin, in the early endosomc in pancreatic β cells and its physiological function in exo-endocytosis of secretory granutes"J Cell Sci. 114・1. 219-227 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Nakamichi., H.Ishida., et al.: "An insulin-related peptide expressed in 3T3L1 adipocytes is localized in GLUT4 vesicles and secreted in response to exogenous insulin, which augments the insulin-stimulated glucose uptake"J Cell Sci. 116. 73-79 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Kimoto., H.Ishida., et al.: "Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide"Biochem Biophys Res Commun. 303. 112-119 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Ohara-Imaizumi., H.Ishida., et al.: "Monitoring of exocytosis and endocytosis of insulin secretory granules in the pancreatic β-cell line MIN6 using pH-sensitive green fluorescent protein (pHuorin) and confocal laser microscopy"Biochem J. 363. 73-80 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Ohara-Imaizumi., H.Ishida., et al.: "Imaging exocytosis of single insulin secretory granules with evanescent wave microscopy - Distinct behavior of granule motion in biphasic insulin release -"J Biol Chem. 277(6). 3805-3808 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Nagamatsu., H.Ishida., et al.: "Adenovirus-mediated preproinsulin gene transfer into adipose tissues ameliorates hyperglycemia in obese diabetic KKAy mice"FEBS lett. 509. 106-110 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Miura., H.Ishida., et al.: "Impairment of insulin-stimulated GLUT4 translocation in skeletal muscle and adipose tissue in the Tsumura Suzuki obese diabetic mouse: a new genetic animal model of type 2 diabetes"Eur J Endocrinol. 145. 785-790 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Ohara-Imaizumi., H.Ishida., et al.: "Mastoparan stimulates GABA release from MIN6 cells -relationship between SNARE proteins and mastoparan action-"Biochem Biophys Res Commun. 289. 1025-1030 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Katahira., H.Ishida., et al.: "A cute inhibition of proinsulin biosynthesis at the translational level by palmitic acid"Biochem Biophys Res Commun. 282. 507-510 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Nagamatsu., H.Ishida., et al.: "Localization of cellubrevin-related peptide, endobrevin, in the early endosome in pancreatic β cells and its physiological function in exoendocytosis of secretory granules"J Cell Sci. 114(1). 219-227 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Fujimoto., H.Ishida., et al.: "Augmentation of basal insulin release from rat islets by preexposure to a high concentration of glucose"Am J Physiol. 279. E927-E940 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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