Physiological and therapeutic roles of PACAP in glucose metabolism and diabetes.
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Accession number;04A0322991
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| Title;Physiological and therapeutic roles of PACAP in glucose metabolism and diabetes. |
| Author;
NAKATA MASANORI
(Jichi Medical School, JPN)
YADA TOSHIHIKO
(Jichi Medical School, JPN)
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Journal Title;Folia Pharmacologica Japonica
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Journal Code:G0740A
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ISSN:0015-5691
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VOL.123;NO.4;PAGE.267-273(2004)
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| Figure&Table&Reference;FIG.4, REF.40 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous neuropeptide in the central and peripheral nervous systems. Previously we reported that PACAP38 is localized in pancreatic islets and serves as an endogenous amplifier of glucose-induced insulin secretion. PACAP activates Gs-cAMP system, stimulates voltage-dependent Ca2+ channels, and increases cytosolic Ca2+ concentration in .BETA.-cells. On the other hand, PAC1 receptor is expressed in adipocytes. PACAP enhances insulin-stimulated glucose uptake in an adipocyte cell-line, 3T3-L1 cells. PACAP does not alter the tyrosine phosphorylation of insulin receptor and IRS-1, but increases the activity of PI-3 kinase, a distal site of insulin signaling. PACAP also promotes differentiation of 3T3-L1 cells from fibroblasts to adipocytes. In GK rats, an animal model of type 2 diabetes, daily i.p. injection of PACAP38 (6 pmol/kg) from the age of 3 weeks prevents development of hyperglycemia between 3 to 8 weeks. These results demonstrate that PACAP enhances glucose-stimulated insulin secretion in islets, enhances insulin action inadipocytes, and prevents hyperglycemia in diabetic animals. This finding presents a possible therapeutic use of PACAP in the treatment of diabetes. (author abst.) |
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