Experimental Research On Molecular Mechanism Of Berberine In Modulating Endoplasmic Reticulum Stress And Improving Insulin Resistance

【Objective】To explore whether berberine modulates the endoplasmic reticulum stress through inhibiting apoptosis in the sub-cellular level to achieve the curative effect on insulin resistance in type 2 diabetic rats.【Methods】Male Wistar rats fed with high fructose diets, were given berberine and 4-Phenyl butyric acid intervention respectively. Biochemical indicators such as FPG, FINS, OGTT, TG, TCH, LDL-C and HDL-C were examined, and isletβ-cell apoptosis were assayed by TUNEL, the expression of apoptosis-related protein ASK-1 and Caspase-12 was detected by immunohistochemisty.【Results】Compared with model group, the serum insulin level in berberine group was reduced, while insulin sensitivity index was improved and ASK-1 expression inhibited. In 4-Phenyl butyric acid treated group the serum insulin level was reduced, and also ASK-1 expression inhibited, but it showed hardly effect on insulin resistance. Both two treated groups could not inhibit the expression of Caspase-12.【Conclusion】Berberine can alleviate insulin resistance which may be related to modulating ER stress through anti-apoptosis by inhibiting ASK-1 expression. Part 2 Improving effects of berberine on the endoplasmic reticulum (ER) stress in MIN6 cells【Objective】To explore whether berberine modulates the endoplasmic reticulum stress through inhibiting the apoptosis in the sub-cellular mechanisms to achieve the curative effect on type 2 diabetes mellitus.【Methods】The insulin secretion of MIN6 cells incubated with berberine and 4-Phenyl butyric acid was determined with glucose-stimulated insulin secretion test. Using MTT assay the potential toxicity of berberine and 4-phenyl butyric acid on MIN6 cells was analyzed and the effects of berberine and 4-phenyl butyric acid on cellular proliferation in endoplasmic reticulum stress model induced by tunicamycin was observed. The expression of apoptosis-related protein ASK-1 and Caspase-12 was detected with immunohistochemisty.【Results】It was demonstrated that berberine and 4-phenyl butyric acid showed hardly effects on the basic and glucose-stimulated insulin secretion. Berberine at the concentration of 100μmol/L significantly inhibited the survival of MIN6 cells. Compared with model group, both berberine and 4-phenyl butyric acid could reduce the rate of MIN6 cells apoptosis, and berberine could further significantly inhibit the expression of ASK-1 and Caspase-12. 4-Phenyl butyric acid could only significantly inhibit the expression of ASK-1.【Conclusion】Berberine can reduce the rate of MIN6 cells apoptosis with ER stress which may be related to the attenuation of ER stress through anti-apoptosis by inhibiting ASK-1 and Caspase-12 expression.