PANCREAS ALERTS

Pancreas 2001; 22:317-25

Effects of Synthetic Serine Protease Inhibitors on Proliferation and Collagen Synthesis of Human Pancreatic Periacinar Fibroblast-Like Cells

Nakamura F, Shintani Y, Saotome T, Fujiyama Y, Bamba T

Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan

The authors have previously reported that human pancreatic periacinar fibroblast-like cells (hPFCs) could be cultured from isolated pancreatic acini which are thought to play a crucial role in pancreatic fibrosis by correlating with the platelet-derived growth factor (PDGF) and the transforming growth factor beta1 (TGF-beta1).

In this study, the effects of synthetic serine protease inhibitors (FOY-007 and FOY-305) on proliferation and collagen synthesis of hPFCs under cytokine stimulation were examined. The cell proliferation and collagen synthesis were evaluated using assays of ³H-thymidine incorporation and procollagen type I c-terminal peptide (PIP), and ¹⁴C-proline incorporation to de novo synthesized collagen, respectively.

The cell proliferation stimulated by the PDGF was inhibited by the application of both FOY-007 in a dose dependently way (1-100 mM) and FOY-305 at 100 mM. FOY-007 attenuated the collagen synthesis and PIP production stimulated by TGF-beta1 dose dependently, but FOY-305 inhibited only PIP production. Both protease inhibitors demonstrated no effect on the proliferation and collagen synthesis of hPFCs when they were not stimulated by PDGF or TGF-beta1.

Serine protease inhibitors act on hPFCs to diminish the effects of PDGF on proliferation and the effects of TGF-beta1 on collagen synthesis.

Pancreas 2001;22:307-10

High Glucose Concentration Favors the Selective Secretion of Islet Amyloid Polypeptide through a Constitutive Secretory Pathway in Human Pancreatic Islets

Gasa R, Gomis R, Casamitjana R, Novials A

Diabetes Unit, Hospital Clinic, Barcelona University, Spain

The authors studied the contribution of the constitutive and the regulated pathways involved in the total secretion of islet amyloid polypeptide (IAPP) in human pancreatic islets after prolonged culture at either 5.5 or 24.4 mM glucose.

In islets cultured in low concentrations of glucose, the secretion of IAPP in response to glucose was unaffected by brefeldin A (BFA) and completely blocked by ethyleneglycoltetraacetic acid. In islets cultured in high glucose concentrations, it was strongly inhibited by both agents. BFA had no effect on the glucose-induced insulin secretion.
The determination of the islet peptide contents and the mRNA levels revealed a many-fold increase in the IAPP/insulin molar ratio of islets cultured in high glucose concentrations.
Thus, prolonged exposure of human islets to high concentrations of glucose results in an increase in the synthesis of IAPP with respect to insulin. As a result, the release of IAPP through a mechanism sensitive to BFA is favored.

The authors concluded that their data support the hypothesis that IAPP and insulin are regulated in a non-coordinated way in human pancreatic islets.