J Korean Diabetes Assoc.  2005 Jul;29(4):304-314.

Pancreatic Stellate Cell Activation by High Glucose and Its Effect on Angiotensin II

• Ko SH
• Hong OK
• Lee MK
• Park EH
• Lee SS
• Ahn YB
• Song KH
• Cha BY
• Son HY
• Kim MJ
• Jung IK
• Yoon KH

Abstract

BACKGROUND: Pancreatic stellate cells (PSCs) are known to be related to pancreatic inflammation and fibrosis, and are the result of extracellular matrix(ECM) protein synthesis. Recent studies have shown that blockade of the renin-angiotensin system (RAS) attenuated pancreatic inflammation and fibrosis. However, there is little data relating to high glucose (HG) and its effects on PSCs. We investigated the effects of HG on ECM protein and angiotensin II(AT II) in PSCs.
METHODS
Isolated PSCs were cultured in HG(D-glucose 5.5(LG), 27.8 mM(HG)) medium. The levels of AT II and TGF-beta were measured using radioimmunoassay, and the AT II-stained cells counted. RT-PCR for the AT II receptor subtypes and Western blot analyses for the expressions of ECM proteins, such as connective tissue growth factor(CTGF) and collagen type IV, were performed. The AT II receptor antagonist, candesartan(10micrometer), and angiotensin converting enzyme inhibitor, ramiprilat(100nM) treatedments were also used.
RESULTS
The thymidine uptake of the PSCs increased 4 times in the HG culture. The AT II levels(LG vs. HG, 17.1+/-4.9 vs. 36.0+/-.2pg/mL, P<0.05) and AT II-stained PSCs (LG vs. HG, 22.5+/-2.0 vs. 39.3+/-11.0%, P<0.05) were significantly increased after 6 hrs under HG conditions. The TGF-beta concentration was also significantly higher under HG conditions(LG vs. HG, 436.3+/-69.0 vs. 1115.1+/-434.0pg/mL, P<0.05) after 72 hrs. After 72 hrs, the protein expressions of CTGF and collagen type IV under HG conditions were significantly increased and effectively attenuated by the candesartan and ramiprilat treatments.
CONCLUSION
A high glucose concentration could significantly increased PSCs proliferation, which also correlated with the AT II production. Consequently, PSCs proliferation was caused by HG induced ECM protein synthesis, and was attenuated by the AT II receptor antagonist. Therefore, pancreatic inflammation and fibrosis could be aggravated by hyperglycemia, and AT II might play an important role in the pathogenesis.

MeSH Terms

Angiotensin II*
Angiotensins*
Blotting, Western
Collagen Type IV
Connective Tissue
Fibrosis
Glucose*
Hyperglycemia
Inflammation
Pancreatic Stellate Cells*
Peptidyl-Dipeptidase A
Radioimmunoassay
Renin-Angiotensin System
Thymidine
Transforming Growth Factor beta
Angiotensin II
Angiotensins
Collagen Type IV
Glucose
Peptidyl-Dipeptidase A
Thymidine
Transforming Growth Factor beta