1996 Fiscal Year Final Research Report Summary
Expression of calcium channel mRNAs in rat pancreatic islets and insulin secretion
Project/Area Number |
07671098
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
内分泌・代謝学
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Research Institution | ASAHIKAWA MEDICAL COLLEGE |
Principal Investigator |
IWASHIMA Yasunori Asahikawa medical college Assitant, 医学部, 助手 (30176549)
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Project Period (FY) |
1995 – 1996
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Keywords | insulin secretion / VDCC / Pancreatic islet / OLETF rat / gene expression / glucose infused rat |
Research Abstract |
Expression of calcium channel mRNAs in rat pancreatic islets and insulin secretion. Expression of the genes for voltage-dependent calcium channels (VDCCs) was studied in pancreatic islets obtained from normal rats, high glucose-infused rats and spontaneously diabetic OLETF rats. A competitive reverse transcriptase-polymerase chain reaction (RT-PCR) procedure was used to obtain quantitative data on the levels of these transcripts in islets obtained from individual rats. The quantitative RT-PCR data indicate that the levels of mRNA encoding the a_1-subunit of the b-cell VDCC are a few fold greater than those for the cardiac subtype. The levels of mRNA for the b_2-subunit of the b-cell VDCC are also 100-150 fold greater than those for the b_3-subunit in normal Wistar, LETO rats and OLETF rats before the onset of diabetes. Glucose infusion for 48 h in normal rats and diabetic hyperglycemia in OLETF rats result in a significant reduction in the levels of mRNA for both the b-cell and cardiac a_1-subunit as well as b_2-and b_3-subunit, and this is associated with enhanced basal secretion but reduced responses to glucose and the Ca^<2+> channel agonist Bay K 8644. In summary, the predominant VDCC a_1-subunit and b-subunit expressed in islets under basal conditions are the b-cell form with lower levels of the cardiac subtype, and the b_2-subunit with lower levels of the b_3-subunit.It appears that hyperglycemia may be the main cause of downregulation of the levels of mRNA encoding the VDCC subunits. At the present time, however, we could not know whether the levels of mRNA for these subunits are regulated at the level of transcription or the stability of mRNA.
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