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1994 Fiscal Year Final Research Report Summary

Physiological and molecular biological studies on functional alterations in ion channels of pancreatic beta cells in diabetes mellitus.

Research Project

Project/Area Number 05670857
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

ISHIDA Hitoshi  Assistant Professor, Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, 医学部, 助手 (80212893)

Co-Investigator(Kenkyū-buntansha) SEINO Yutaka  Associate Professor, Department of Metabolism and Clinical Nutrition, Kyoto Univ, 医学部, 助教授 (40030986)
Project Period (FY) 1993 – 1994
KeywordsDiabetes mellitus / Pancreatic beta-cells / Insulin secretion / Intracellular calcium concentration / Patch-clamp technique / ATP-sensitive K^+ channels / Voltage-dependnet Ca^<2+> channels
Research Abstract

The selective impairment of glucose-induced insulin secretion has been known as one of the major characteristics of pathogenetic aspects in non-insulin-dependent diabetes mellitus (NIDDM) . We have recently reported that the intracellular calcium responses to glucose are selectively impaired in pancreatic beta cells of NIDDM rat models. In order to clarify the molecular mechanism underlying this impairment, we investigated the activities of ATP sensitive K^+ channels (K_<ATP> channels) and voltage-dependent Ca^<2+> channels (VDCCs) directly using the patch-clamp technique, both of which are known to play an important role in the elevation of intracellular calcium levels after the glucose stimulation. The inhibition of K_<ATP> channels activities by glucose was reduced in beta cells of GK rats, a genetic model of NIDDM,whereas the ATP sensitivity of channels was intact. This clearly indicates that the intracellular glucose metabolism is impaired in NIDDM beta cells. On the other hand, the channels inhibition by glyceraldehyde or ketoisocaproate, which are matabolizad through the intermediates in glucose metabolism, was similar between GK and control rats. However, the inhibition of channel activities by dihydroxyacetone (DHA) -phosphate, an isomer of glyceraldehyde-3-phosphate, was reduced in NIDDM beta cells. Since DHA-phosphate can enter the glycerol phosphate shuttle which is thought to be a direct link in the metaolic pathway between glycolysis and mitochondrial oxidation, the responsible sites for impaired glucose metabolism is speculated to be located in this shuttle. In addition, the direct augmentation of VDCC activities through glucose metabolism was also found to be reduced by perforated-patch recording in beta cells of GK rats. These facts are though to be closely related to the selective impairment of glucose induced insulin secretion from NIDDM beta cells.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Y.Tsuura,et al.: "Reduced sensitivity of dihydroxyacetone on ATP-sensitive K^+ channeles of pancreatic beta cells in GK rats." Diabetologia. 37. 1082-1087 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Kato,et al: "Increased calcium channel currents of pancreatic β cells in neonatally streptozocin-induced diabetic rats." Metabolism. 43. 1395-1400 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Tsuura,et al: "Nitric oxide opens ATP-sensitive K^+ channels through suppression of phosphofructokinase activity and inhibits glucose-induced insulin release in pancreatic β cells." J Gen Physiol. 104. 1079-1098 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Masuda,et al: "Effects of Troglitazone(CS-045)on insulin secretion in isolated rat pancreatic islets and HIT cells:an insulinotropic mechanism distinct from glibenclamide." Diabetologia. 38. 24-30 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Okamoto,et al.: "Hyperresponse in calcium-induced insulin release from electrically permeabilized pancreatic islets of diabetic GK rats and its defective augmentation by glucose." Diabetologia. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Inagaki,et al.: "Expression and role of ionotropic glutamate receptors in pancreatic islet cells." FASEB J. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ishida,et al.: "Functional alterations in the intracellular calcium signaling system and ion channels of pancreatic B-cells in non-insulin-dependent diabetes mellitus." Frontirrs of Insulin Secretion and Pancreatic B-cell Research P.R.Flatt and S.Lanzen(eds)(in press),

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Tsuura, et al.: "Reduced sensitivity of dihydroxyacetone on ATP-sensitive K^+ channels of pancreatic beta cells in GK rats." Diabetologia. 37. 1082-1087 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Kato, et al.: "Increased calcium channel currents of pancreatic beta cells in neonatally streptozocin-induced diabetic rats." Metabolism. 43. 1395-1400 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Tsuura, et al.: "Nitric oxide opens ATP-sensitive K^+ channels through suppression of phosphofructokinase activity and inhibits glucose-induced insulin release in pancreatic beta cells." J Gen Physiol. 104. 1079-1098 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Masuda, et al.: "Effects of Troglitazone (CS-045) on insulin secretion in isolated rat pancreatic islets and HIT cells : an insulinotropic mechanism distinct from glibenclamide." Diabetologia. 38. 24-30 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Okamoto, et al.: "Hyperresponse in calcium-induced insulin release from electrically permeabilized pancreatic islets of diabetic GK rats and its defective augmentation by glucose." Diabetologia. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Inagaki, et al.: "Expression and role of ionotropic glutamate receptors in pancreatic islet cells." FASEB J. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ishida, et al.: Frontiers of Insulin Secretion and Pancreatic beta-cell Research P.R.Flatt and S.Lanzen (eds). Functional alterations in the intracellular calsium signaling system and ion channels of pancreatic beta-cells in non-insulin-dependent diabetes mellitus. (in press),

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

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Published: 1996-04-15  

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