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Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-cells in Mild and Severe Experimental Rodent Model of chronic Pancreatitis

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Open journal of Endocrine and Metabolic Diseases 2024年第2期14卷 53-72页

作者： Galande Sheethal Ranjeet K. Tokala Pavan Pondugala Krishna Vemula Vijayalakshmi Venkatesan Pothani Suresh Surya Satyanarayana Singh Guduru Venkat Rao Duvvur Nageshwar Reddy Mitnala Sasikala Basic Science and Translational Research Division Asian Healthcare Foundation AIG Hospitals Hyderabad India Division of cell and Molecular Biology National institute of Nutrition Hyderabad India National Animal Resource Facility for Biomedical Research Hyderabad India Department of Biochemistry Osmania University Hyderabad India Department of Surgical Gastroenterology Asian Institute of Gastroenterology Hyderabad India Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India

chronic pancreatitis (cP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of cP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of cP. Dietary intervention of epigallocatechin-3-gallate (EGcG) was tested in both the models of cP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in cP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGcG dietary intervention in cerulein model of cP and 1.6-fold in L-arginine model of cP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGcG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGcG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

关键词： Dietary Intervention c57bl6/j mice Epigallocatechin-3-Gallate N-Acetyl cysteine curcumin chronic Pancreatitis Islets Glucose Stimulated Insulin Secretion

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