| Objective: Many researches have certificated that the pathogenesy of type 2 diabetes mellitus(T2DM) refers to two aspects, the insulin deficiency and insulin resistance(IR). IR is the most important agent of T2DM. The key peripheral target organs of IR are skeletal muscle, liver, and adipose tissue. Investigation of recent years founds that adiponectin which is the abundant adipocyte-derived protein hormone possess improving insulin sensitivity, it also possesses anti- hyperglycemia, anti-hyperlipemia, anti-hypertension, anti- inflammatory and anti-atherogenic. Study has certificated that adiponectin activates PPAR and AMPK by binding with AdipoR. Adiponectin receptors (AdipoR1/2) have been cloned by Yamauchi for the first time in 2003. AdipoR1 is primarily expressed in skeletal muscle and adipose tissue and has a wide distribution throughout the organism, AdipoR2 is primarily expressed in the liver. AdipoR1 has a high affinity for globular adiponectin and a very low affinity for the full-length variant. AdipoR2 has a moderate affinity for both forms of adiponectin. Rosiglitazone is one of thiazolidinediones(TZDs) which are insulin sensitizing agents. It can selectively upregulate peroxisome-proliferator-activated receptor-γ(PPAR-γ). Rosiglitazone activates PPAR-γthen lowers circulating levels of glucose and lipids and enhances insulin sensitivity.In this study, T2DM rat model was copied by giving Sprague-Dawlay (SD) rats high-sugar-fat diet and a low dose of streptozotocin(STZ). This model had some characteristics of IR, hyperglycemia and hyperlipidemia, which were similar to those of human T2DM. Then the serum adiponectin content and the AdipoR1 protein expression in skeletal muscle were detected in order to discuss the association between adiponectin, AdipoR1 in skeletal muscle and IR in T2DM rats. Furthermore, rosiglitazone was given to experimental rats to explain the mechanism of the TZDs improving insulin sensitivity of T2DM rats.Methods: 10 of 40 SD rats were taken out randomly to be normal control rats (group A) and the rest were taken for test rats. The control rats were fed with general diet while the test rats were fed with high-sugar-fat diet. 4 weeks later, IR was induced in test group, then STZ 30 mg/kg was injected into abdominal cavity to destroy pancreas. At the end of 6 weeks, the rats whose fasting blood glucose (FBG) was greater than 7.8 mmol/L and insulin sensitivity decreased were considered as T2DM rats. T2DM rats were divided randomly into 2 groups: T2DM model rats (group B), T2DM model rats treated with rosiglitazone (group C). The experiment lasted 18 weeks. At the end of 4 and 6 weeks, body weight, FBG, fasting insulin (FINS), insulin sensitivity index (ISI), serum triglyceride (TG) and total cholesterol (TC) in different group rats were measured. At the end of this experiment, FBG, FINS, ISI, and TG, TC, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) were detected. The microstructure and ultrastructure of skeletal muscle were observed with light and electron microscopes. Serum adiponectin was measured by enzyme-linked immunosorbent assay (ELISA). The protein expression of AdipoR1 in skeletal muscle was detected by immunohistochemical staining. The results were analyzed with computer image-analysis system and the integral optical density (IOD) counts of AdipoR1 were calculated. The data were dealt with SPSS 11.0.Results1 Various indexes after 4 weeks: Been fed with high- sugar-fat diet for 4 weeks, test rats were heavier than normal control rats (P<0.05). FBG(6.33±0.65)mmol/L, FINS 30.19(29.05, 31.65) mIU/L, TG, TC in test rats were higher than FBG(5.13±0.46)mmol/L, FINS 19.45(17.99, 20.99) mIU/L, TG, TC in control rats (all P<0.01). At the same time, ISI 0.0053(0.0050, 0.0054) in test rats was lower than ISI 0.0101 (0.0100, 0.0102) in control rats (P<0.01).2 Various indexes after 6 weeks: 2 weeks after STZ injection, FINS 18.79(18.23, 19.29) mIU/L in test rats compared to FINS 18.35(17.95, 18.98) mIU/L in control rats was unstatistics distinction (P>0.05). Other features were retained. FBG(13.18±1.47) mmol/L in test rats was higher than FBG(5.04±0.46) mmol/L in control rats and ISI 0.0048(0.0045, 0.0053) in test rats was lower than ISI 0.0106(0.0103, 0.0112) in control rats (both P<0.01). Thus far, the T2DM rat model was accomplished.3 Various biochemical indexes after 18 weeks: When the experiment was finished, FBG, FINS and ISI in group A rats were(4.89±0.35) mmol/L, 17.66(16.83, 18.27) mIU/L and 0.0111(0.0104, 0.0121). FBG(12.43±1.48) mmol/L, FINS 20.95(19.81, 22.11) mIU/L, TG, TC, LDL-C and VLDL-C in group B rats were all higher than those in group A rats. HDL-C and ISI 0.0039(0.0036, 0.0041) in group B rats were lower than those in group A (all P<0.05). FBG(9.01±1.14) mmol/L , FINS 18.45(17.97, 18.76) mIU/L and foregoing items in group C rats were lower than those in group B rats, HDL-C and ISI 0.0065(0.0057, 0.0069) in group C rats were higher than those in group B rats (all P<0.05).4 the serum adiponectin: At the end of 18weeks, serum adiponectin (1.01±0.27)μg/mL in group B rats was lower than that (1.73±0.32)μg/mL in group A rats (P<0.05). And foregoing item (1.34±0.43)μg/mL in group C rats was higher than that in group B rats. (P<0.01). Related analysis showed that serum adiponectin had a negative correlation with FBG, FINS and LDL-C (r=-0.656, -0.359 and -0.637, all P<0.01), a positive correlation with HDL-C and ISI (r=0.614 and 0.615, both P<0.01) in experimental rats.5 The protein expression of AdipoR1 in skeletal muscle: The IOD(106.02±25.70) of AdipoR1 in group B rats was 47.2% of that(224.81±58.19) in group A rats. The IOD(151.47±30.63) of AdipoR1 in group C rats was 1.43 times of that in group B rats (all P<0.05). Related analysis showed that AdipoR1 expression had a negative correlation with FBG, FINS, and LDL-C (r=-0.712, -0.437 and -0.763, all P<0.01), a positive correlation with HDL-C, ISI (r=0.781, 0.725, both P<0.01) in experimental rats.6 Morphology: HE staining showed that skeletal muscle fiber of every group rats was in order, the morphology of karyon and intercellular space were normal. The skeletal muscle ultrastructure of every group rats appeared that myofibril was in order, sarcomere was Integrity, light and dark band was clear, the configuration and quantity of mitochondrion was normal, the quantity and distribution of amylon was also nomal.Conclusions1 The T2DM rat model that was induced by high-sugar-fat diet and a low dose of STZ had some characteristics similar to human T2DM. It would be available to study T2DM and its complications.2 The serum adiponectin and the AdipoR1 protein expression in skeletal muscle of T2DM rats were decreased. It indicated that adiponectin and AdipoR1 had a tight association with hyperglycemia, hyperlipemia, IR and T2DM. It illuminated that the study on adiponectin, AdipoR1 and theirs activator might afford new theory to prevent and treat of T2DM and IR.3 Rosiglitazone could increase serum adiponectin concentration and AdipoR1 protein expression in skeletal muscle, then lowered circulating levels of glucose and lipids and improved insulin sensitivity.
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