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Conophylline Suppresses Pancreatic Stellate Cells and Improves Islet Fibrosis in Goto-Kakizaki Rats.
MedLine Citation:
PMID:  22202163     Owner:  NLM     Status:  Publisher    
Activin A is a differentiation factor for β-cells and is effective to promote β-cell neogenesis. Activin A is also an autocrine activator of pancreatic stellate cells, which play a critical role in fibrogenesis of the pancreas. Conophylline (CnP) is a natural compound, which reproduces the effect of activin on β-cell differentiation and promotes β-cell neogenesis when administered in vivo. However, its effect on stellate cells is not known. We therefore investigated the effect of CnP on stellate cells both in vitro and in vivo. Unlike activin A, CnP inhibited activation of cultured stellate cells and reduced the production of collagen. We then analyzed the involvement of stellate cells in islet fibrosis in Goto-Kakizaki (GK) rats, a model of type 2 diabetes mellitus. In pancreatic sections obtained from 6-wk-old GK rats, CD68-positive macrophages and glial fibrillary acidic protein- and α-smooth muscle actin-positive stellate cells infiltrated into islets. Later, the number of macrophages was increased, and the α-smooth muscle actin staining of stellate cells became stronger, indicating the involvement of stellate cells in islet fibrosis in GK rats. When CnP was administered orally for 4 wk, starting from 6 wk of age, invasion of stellate cells and macrophages was markedly reduced and islet fibrosis was significantly improved. The insulin content was twice as high in CnP-treated rats. These results indicate that CnP exerts antifibrotic actions both in vitro and in vivo and improves islet fibrosis in Goto-Kakizaki rats.
Rie Saito; Satoko Yamada; Yoritsuna Yamamoto; Tsutomu Kodera; Akemi Hara; Yuji Tanaka; Fumihiko Kimura; Izumi Takei; Kazuo Umezawa; Itaru Kojima
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-27
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute for Molecular and Cellular Regulation (R.S., S.Y., Y.Y., T.K., A.H., I.K.), Gunma University, Maebashi 371-8512, Japan; Third Department of Medicine (R.S., Y.Y., T.K., F.K.) and Department of General Medicine (Y.T.), National Defense Medical College, Saitama-Ken 359-8513, Japan; Department of Internal Medicine (I.T.), Tokyo Dental University, Tokyo 113-8510, Japan; and Keio University School of Science and Technology (K.U.), Tokyo 108-8345.
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