Conophylline suppresses pancreatic stellate cells and improves islet fibrosis in Goto-Kakizaki rats.

Abstract

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.

• Authors: Rie Saito, Satoko Yamada, Yoritsuna Yamamoto, Tsutomu Kodera, Akemi Hara, Yuji Tanaka, Fumihiko Kimura, Izumi Takei, Kazuo Umezawa, Itaru Kojima
• Journal: Endocrinology (Endocrinology) Vol. 153 Issue 2 Pg. 621-30 (Feb 2012) ISSN: 1945-7170 [Electronic] United States
• PMID: 22202163 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Vinca Alkaloids
• conophylline
• Collagen
• Glucose

Topics

• Animals
• Blood Glucose
• Cells, Cultured
• Collagen (metabolism)
• Fibrosis (drug therapy)
• Gene Expression Regulation (drug effects)
• Glucose (metabolism)
• Islets of Langerhans (drug effects, pathology)
• Male
• Pancreas (drug effects, metabolism, pathology)
• Pancreatic Stellate Cells (drug effects, metabolism)
• Rats
• Rats, Inbred Strains
• Vinca Alkaloids (pharmacology)