TITLE:
Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis
AUTHORS:
Galande Sheethal, Ranjeet K. Tokala, Pavan Pondugala, Krishna Vemula, Vijayalakshmi Venkatesan, Pothani Suresh, Surya Satyanarayana Singh, Guduru Venkat Rao, Duvvur Nageshwar Reddy, Mitnala Sasikala
KEYWORDS:
Dietary Intervention, C57BL6/J Mice, Epigallocatechin-3-Gallate, N-Acetyl Cysteine, Curcumin, Chronic Pancreatitis, Islets, Glucose Stimulated Insulin Secretion
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.14 No.2,
February
26,
2024
ABSTRACT: 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.