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2002 Fiscal Year Final Research Report Summary

Physiological role of NO produced by constitutive NO synthase in pancreatic islet of Langerhans

Research Project

Project/Area Number 13670094
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionUniversity of Shizuoka

Principal Investigator

ISHIKAWA Tomohisa  Ph. D. Dept of Pharmacology, Sch of Pharmaceutical Sciences, Univ of Shizuoka; Associate Phofessor, 薬学部, 助教授 (10201914)

Project Period (FY) 2001 – 2002
Keywordsislet of Langerhans / β-cells / rat / NO / NO synthase / Ca^<2+> / glucose / DAF-2
Research Abstract

METHODS: Pancreatic islets of Langerhans and β cells were isolated from male Wistar rats (9-12 weeks old) by collagenase digestion technique. (1) Double immunostaining with antiserum to NOS1 or NOS3 and that to glucagon, insulin, somatostatin, or pancreatic polypeptide was performed in the isolated islets, and the fluorescent images were analyzed in a confocal laser scanning microscope. (2) The production of NO was measured with the fluorescent NO indicator DAF-2 DA in a confocal laser scanning microscope. (3) [Ca^<2+>]i was measured in fura-PE3-loaded β cells by Argus-50/CA system. (4) The secretion of insulin from isolated islets was measured by the batch incubation method and EIA. (5) ATP-sensitive K^+ currents were measured by the patch clamp method.
RESULTS AND DISCUSSION: (1) Double immunostaining showed that both NOS1- and NOS3-immunoreactivity are present in rat β celles. (2) Glucose produced NO in the β cells in a concentration-dependent manner. (3) In the presence of L-NNA, the NO donor NOC7 at 0.5 and 1.0 μM increased the amplitude of [Ca^<2+>]i oscillations induced by 11.1 mM glucose, and at 10 μM terminated them. A soluble guanylyl cyclase inhibitor suppressed the stimulatory action of NOC7 at low concentrations, whereas it did not affect the inhibitory one at high concentrations, suggesting that the former is mediated by cGMP but the latter is not. (4) Insulin secretion induced by 11.1 mM glucose was facilitated by 0.5 μM NOC7, whereas it was suppressed by 10 μM NOC7.
CONCLUSION: NO is an endogenous regulator of insulin secretion, which facilitates and inhibits glucose-induced insulin secretion at low and high concentrations, respectively

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Sugino, F. et al.: "Inhibition by nitric oxide of Ca^<2+> responses in rat pancreatic α-cells"Life Sci. 71. 85-93 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishikawa, T. et al.: "Non-contribution of renin-angiotensin system to pressor response to N^G-nitro-L-arginine in dogs"Fundam Clin Pharmacol. 16. 15-21 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakayama, K. et al.: "Interactive role of tyrosine kinase, protein kinase C, and Rho/Rho kinase systems in the mechanotransduction of vascular smooth muscles"Biorheology. 40. 307-3141 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishikawa, T. et al.: "Two distinct effects of cGMP on cytosolic Ca^<2+> concentration of rat pancreatic β-cells"J Pharmacol Sci. 91. 41-46 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaneko, Y. et al.: "Dual effect of nitric oxide on cytosolic Ca^<2+> concentration and insulin secretion in rat pancreatic β-cells"Am J Physiol Cell Physiol. 284. C1215-C1222 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugino F., Ishikawa T., Nakada S., Kaneko Y., Yamamoto Y., Nakayama K.: "Inhibition by nitric oxide of Ca^<2+> responses in rat pancreatic α-cells"Life Sci.. 71. 85-93 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa T., Nejishima H., Imamura T., Nakayama K.: "Non-contribution of renin-angiotensin system to pressor response to N^G-nitro-L-arginine in dogs"Fundam Clin Pharmacol. 16. 15-21 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakayama K., Obara K., Tanabe Y., Saito M., Ishikawa T., Nishizawa S.: "Interactive role of tyrosine kinase, protein kinase C, and Rho/Rho kinase systems in the mechanotransduction of vascular smooth muscles"Biorheology. 40. 307-314 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishikawa T., Kaneko Y., Sugino F., Nakayama K.: "Two distinct effects of cGMP on cytosolic Ca^<2+> concentration of rat pancreatic β-cells"J. Pharmacol Sci.. 91. 41-46 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaneko Y., Ishikawa T., Amano S., Nakayama K.: "Dual effect of nitric oxide on cytosolic Ca^<2+> concentration and insulin secretion in rat pancreatic β-cells"Am J. Physiol Cell Physiol. 284. C1215-C1222 (2003)

    • 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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