| [BACKGROUD AND OBJECTIVE]Insulin resistance (IR) and metabolic diseases has a close relationship. IR is not only thepathophysiological basis of type2diabetes but also a “common soil†of metabolic syndrome.And a large number reported in the literature: an important part of glucose utilizationdamage in relation to IR, the IR state, the peripheral tissue glucose uptake and utilizationwere significantly reduced. Therefore, it is important significance that improving peripheraltissue glucose uptake and utilization to improve IR. It is may also become an importantmeans of prevention and treatment of type2diabetes.Arecoline is an alkaloid and extracted from natural plant betel, its wide range ofbiological functions, has deworming, sterilization, antithrombotic,anti-atherosclerosis andother function. My room early studies have shown that low doses of arecoline can improveglucose and lipid disorders in type2diabetic rat liver and found that low doses of arecolinecan protect pancreatic beta cells, inhibit the expression of wing-helix transcription factor O1(The FoxO1); while high doses of arecoline with liver toxicity. We can see the arecolineimprovement in insulin resistant rats may be associated with increased insulin sensitivity.Insulin resistance (IR) is caused by disorders of carbohydrate metabolism: reduced isletsensitive and impaired glucose utilization to peripheral tissue. Skeletal muscle is animportant organization to the use of glucose and maintain blood sugar balance, about80%ofinsulin stimulated by glucose uptake by skeletal muscle, Occupies an important position inthe insulin resistance in skeletal muscle.Therefore, this study is to observe the5mg/kg arecoline on skeletal muscle, and toexplore that it is improvement insulin resistance of molecular mechanism in skeletal muscle.[METHODS] 1) A insulin resistant rat model was established by feeding with high fructose diet;2) Fasting blood glucose (FBG) and fasting serum insulin (FSI) were measured byHI-TACH717automatic biochemistry analyzer and radioimmunoassay respectively.3) The mRNA expression of GLUT4and IRS-1in thoracic aorta was analyzed byreverse transcription polymerase chain reaction (RT-PCR) in different group.4) Western blot analysis of arecoline on the organization of GLUT4, p-PI3K, p-Akt,IRS-1protein expression in rat skeletal muscle.[RESULTS]1．Effects of arecoline on fast blood glucose (FBG), fasting blood serum (FSI) and insulinsensitivity index (ISI) in IR rats：Compared with normal group, level of FBG and FSIwere significantly increased, while the ISI was significantly decreased in IR rats；Compared with IR group, arecoline treatment of IR rats can significantly reduce level ofFBG and FSI, increased the level of the ISI in IR rats.2. Effects of arecoline on IRS-1protein and gene in skeletal muscle of IR rats：Comparedwith normal group, expression of IRS-1protein and gene was significantly reduced inskeletal muscle of IR rats；Compared with model group, in skeletal muscle ofIR,expression of IRS-1protein and gene were significantly up-regulated with arecolinetreatment of IR rats.3. Effects of arecoline on p-PI3K protein and p-Akt protein in skeletal muscle of IR rats：Compared with normal group, expression of p-PI3K and p-Akt protein was significantlyreduced in skeletal muscle of IR rats; Compared with model group, arecoline treatmentof IR rats can significantly up-regulate the expression of p-PI3K and p-Akt protein inskeletal muscle of IR rats.4. Effects of arecoline on GLUT4protein and gene in skeletal muscle of IR rats:Comparedwith normal group, expression of GLUT4protein and gene was significantly reduced inskeletal muscle of IR rats;Compared with model group, in skeletal muscle ofIR,expression of GLUT4protein and gene were significantly up-regulated witharecoline treatment of IR rats. [Conclusion]The arecoline improve insulin resistance in skeletal muscle of rats by activation ofIRS-1/PI3K/Akt signaling pathway and up-regulation of GLUT4expression in skeletalmuscle. |
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