Abstract
Background
Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type 2 diabetes, lacks the
expression of cholecystokinin-1 receptor mRNA and exhibits inflammation and degeneration
of the pancreas and eventually develops insulinopenic diabetes. Protease inhibitors
are known to modulate inflammatory response and fibrosis as well as inhibit proteases
activity.
Aim
To examine the effects of long-term treatment with camostat, a synthetic protease
inhibitor, on metabolic and histopathological changes in the islets of OLETF rats.
Method
OLETF rats were fed either camostat-containing food (200 mg/100 g) from 12 or 28 weeks
of age to 72 weeks of age, or fed standard rat diet.
Results
Camostat-fed rats gained less weight or lost weight, although they consumed more food
than the control rat when food intake was adjusted for body weight. Camostat reduced
visceral adipose depots and fasting serum concentrations of triglyceride, free fatty
acids, cholesterol, glucose, and insulin. Pancreatic insulin content in camostat-treated
rats was significantly higher than in control rats. Immunohistochemistry revealed
marked suppression of expressions of tumor necrosis factor α, interleukin 1β, interleukin 6, and α-smooth muscle actin in the islets of camostat-treated rats, compared with control
rats. Histologically, disruption of the islets and pancreatic fibrosis were noted
in control rats but not in camostat-fed rats.
Conclusion
Our findings suggest that camostat prevents and reverses obesity, hyperinsulinemia,
hyperglycemia, and hyperlipidemia and markedly inhibits inflammation, fibrosis, and
disruption of the islets in the genetically obese diabetic OLETF rats.
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Article info
Publication history
Accepted:
December 17,
2004
Received:
April 3,
2004
Identification
Copyright
© 2005 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
