The Study On The Molecular Mechanism Of The Adipose Tissue As Targeting Tissue During The Course Of Diabetes's Therapy Of Berberine

Obesity and insulin resistance are more important health problem. The main features of adult obesity are the hypertrophy of adipocyte and the increase in the number of adipocyte. Adipose tissues are important organ which regulates glucose and lipid metabolism and the center of endocrine, paracrine and autocrine signals. Dysfunction of adipose tissues (adipose tissue insulin resistance) will lead to maladjustment of lipid metabolism in body which exhibit dyslipidomia and ectopic fat deposition in non-adipose tissues.Recently the antidiabetic characteristic of berberine is the hotspot of its pharmacology study. However, as an insulin-sensitizing drug, the therapeutic effect of berberine on adipose tissue insulin resistance is still unclear. In our study, we use the method which low-dose STZ was given based on high fat diet to induce type 2 diabetic hamster model. After that we mainly study the remedial effects of berberine on molecular mechanisms which lead to changes in isulin sensitivity of adipose tissues.The results indicated that berberine not only can improve hyperglycemia and dyslipidemia in diabetic states but also improve ectopic viscera fat deposition and ratio of big adipocyte in adipose tissues of type 2 diabetic hamsters to reverse ectopic fat deposition in non-adipose tissues and improve insulin resistance.Based on the results of microarry, we use the method of real-time PCR to study the gene change of adipose tissue in diabetic hamsters and berberine-treated diabetic hamsters. The results indicated the abnomal expression of SREBPs and its target genes, PPARa and its target genes, HSL, ATGL, GLUT, HK, ATP synthase, the decrease of adponectin and the increase of TNFαand IL-6 in adipose tissues of type 2 diabetic hamsters. After the treatment of berberine, the expression of SREBPs and its target genes, HSL and ATGL is decreased,that indicated berberine inhibit the synthesis and hydrolyzation/lipolysis of fat in adipose tissues of diabetic hamsters. At the same time, the expression of PPARa and its target genes, GLUT, HK and ATP synthase is increased, that indicated berberine help to uptake and metabolism of glucose and promote the oxidation of fatty acids and restore the Mitochondria function in adipose tissues. Berberine also induces the expression of adiponectin and reduces the expression of TNFaand IL-6, that indicate Berberine can improves endocrine function of adipose tissue and the state of chronic and lower inflammation of diabetes.In a word, berberine can effectively improve abnormal metabolism and function of adipose tissues under diabetic states, further improve dyslipidemia and ectopic fat deposition and insulin sensitivity to exhibit its therapeutic effect on type 2 diabetic mellitus. So adipose tissues are one of important common target tissues for berberine therapeutic effect to reduce blood glucose and improve insulin resistance.