| ObjectiveTo investigate the therapeutic effect of "Jiawei Shuilu Erxiandan" on insulin resistance of type 2 diabetes mellitus rat model, and reveal some of the mechanisms.MethodsA rat model of T2DM was established applying STZ-fed method,and the Sprague-Dawley rats were divided randomly into six groups, with 7 rats in each group as followed:normal control (NC), diabetic control (DBC), diabetic group with RSG, diabetic group with traditional Chinese medicine (TCM/low,medium,high doses). rosiglitazone as a positive control drug.Observation of glucose and lipid metabolism, glucose tolerance, insulin sensitivity skeletal muscle pathological and other effects.And in order to understand the molecular mechanism, measurement IRS-1, PI3K p85, GLUT4 mRNA and protein expression level in skeletal muscle tissue.Results①Glucose and lipid metabolism, the model group compared with normal group, FPG significantly increased and glucose tolerance test was significantly abnormal. Jiawei Shuilu Erxiandan with a certain degree of FPG lowering effect, and can significantly reduce blood sugar in diabetic rats after the load increases, improved glucose tolerance (OGTT test showed that the concentration curve TCM group was significantly lower than other groups), while there are some differences in HOMA-IR and western medicine group, and thus play its inhibition of glucose toxicity, and delaying the development of T2DM and duration of the IR. In this study, the model group’s TC, TG, LDL levels were significantly higher compared to normal controls and tissue selection process can be clearly observed in liver tissue there is a lot of fat granule or fat mass, and fat liver lesions have appeared, model group showed the presence of rat liver lipid metabolism disorders. After four weeks of drug intervention, Jiawei Shuilu Erxiandan can reduce TC, TG and LDL levels, little effect to HDL, most obvious effect can sees in the medium and low concentration. And visually observed to varying degrees of liver steatosis.Thus, Jiawei Shuilu Erxiandan with improved lipid metabolism, inhibition of IR process, while improving the role of T2DM and its complications.②Immunohistochemistry, the model group rat skeletal muscle tissue phosphorylation of IRS-1 Ser307 significantly enhanced, while significantly decreased IRS-lprotein expression, suggesting that low-dose STZ plus high fat and high calorie diet can induce stimulation of peripheral tissues of rat IRS-1 serine phosphorylation, reduce the expression of IRS-1 protein expression of downstream signaling molecules P13K p85 and GLUT4 protein was significantly reduced. T2DM rats peripheral tissues, less insulin-stimulated GLUT4 translocation to the cell membrane, thereby affecting glucose uptake in peripheral tissue cells, resulting in the generation of IR. Rosiglitazone and Jiawei Shuilu Erxiandan interventions can partially reverse these changes, manifested in inhibition of phosphorylation of IRS-1 Ser307, improve IRS-1, PI3K expression, and promote GLUT4 translocation to the cell membrane, so improve the utilization of glucose in peripheral tissues thereby improving insulin resistance.③Gene and protein expression levels, the study by RT-PCR and western blot method to detect surface and Jiawei Shuilu Erxiandan comparison with the T2DM rat on skeletal muscle’s IRS-1, PI3K p85, GLUT4 mRNA expression and protein content, with the model group the results showed that Jiawei Shuilu Erxiandan medium dose group could promote IRS-1, PI3K p85, GLUT4 mRNA and protein expression changes between skeletal muscle tissue is the same direction. After drug intervention played an insulin sensitizer effect, can significantly increase the skeletal muscle and adipose tissue GLUT4 mRNA expression, increase protein levels, suggesting Jiawei Shuilu Erxiandan possibly through increased IRS-1 mRNA and protein expression, mediated P13K signal pathway, which initiates GLUT4 downstream gene transcription, increase GLUT4 protein levels, so that the translation of glucose transporter increased ability of cells to transport glucose to enhance and improve the IR of T2DM rats.ConclusionsJiawei Shuilu Erxiandan can improve T2DM rats with lipid disorders, improve insulin sensitivity; and its skeletal muscle histopathology; By increasing IRS 1-mRNA and protein expression in skeletal muscle, mediated IRS-1/P13K/GLUT4 pathway, thus enhancing the transcription of genes downstream of GLUT4, glucose transport capacity of the cells increases, and ultimately improve IR in type 2 diabetic rats.It was highlighted that Jiawei Shuilu Erxiandan was of great value to be developed into effective drug for treatment of T2DM. |
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