Effects of liraglutide on adiponectin and insulin resistance in rats with non-alcoholic fatty liver disease

AIM：To investigate the effects of glucagon-like peptide 1 analog, liraglutide, on adiponectin and insulin resistance in the rats with diet-induced non-alcoholic fatty liver disease (NAFLD). METHODS：Male rats were randomly divided into 3 groups:normal diet (ND) group (n=10), high-fat diet (HFD) group (n=10), and HFD with intraperitoneal injection of liraglutide group (n=10, first 12 weeks with HFD, later 4 weeks with liraglutide). All treatments continued for 16 weeks, and then the rats were killed ethically and the blood samples and liver tissues were collected. The levels of alanine aminotransferase (ALT), fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) were detected by a biochemical automatic analyzer. The levels of free fatty acids (FFAs), fasting insulin (FINS) and adiponectin were measured by RIA and ELISA. RESULTS：Compared with HFD group, the body weight, liver index, homeostasis assessment-insulin resistance (HOMA-IR), the serum levels of TG, TC, ALT and FBG, and the liver levels of TG, TC and FFAs in the rats in liraglutide group were apparently lower, the degree of hepatic steatosis and inflammatory activity significantly decreased (P<0.05), and the level of adiponectin in the serum and liver homogenate increased ob-viously (P<0.05). The level of adiponectin in the liver homogenate was negatively correlated with the levels of FFAs in the liver homogenate. CONCLUSION:Liraglutide is beneficial for NAFLD rats to improve insulin resistance and reduce hepatic steatosis by increasing the level of adiponectin in the serum and liver tissues.     

Correlation of serum omentin-1 level and insulin resistance in rats

AIM：To establish the insulin resistance rat model for evaluating the correlation of omentin-1 level and insulin resistance. METHODS：SPF male Wistar rats (n=30) were randomly divided into normal control group (NC, n=15) and high-fat diet group (HF, n=15). The rats in NC group were fed with basic diet. The insulin resistant model was established by feeding the rats with high-fat diet in HF group. After 10 weeks, 5 rats in each group were assessed by the technique of hyperinsulinaemic-euglycaemic clamp. After the insulin resistant model was successfully established, the body weight and fasting blood glucose were detected. The concentration of fasting serum omentin-1 was analyzed by ELISA. Fasting serum insulin was measured by radioimmunoassay. RESULTS：No difference of fasting blood glucose between the 2 groups was observed. The level of fasting serum insulin in HF group was significantly higher than that in NC group (P<0.05). The level of serum omentin-1 in HF group were significantly decreased compared with NC group (P<0.01). Pearson’s correlation analysis showed that negative correlations between serum omentin-1 and fasting serum insulin (r=-0.654,P<0.01), serum omentin-1 and free fatty acid (r=-0.446, P<0.05) was found. CONCLUSION：In rats, serum omentin-1 level began to decrease at insulin resistance stage. As serum omentin-1 level decreased, the basal insulin level increased, indicating that decreased serum omentin-1 level may be an early factor of IR, diabetes and cardiovascular diseases.     

Effects of glycine on insulin resistance and cognitive impairment induced by high-fructose diet

AIM: To investigate the role of intestinal endotoxemia (IETM) in insulin resistance (IR) and cognitive impairment, and to explore the protective mechanisms of glycine in rats with high-fructose diet. METHODS: The rats in model group were fed with 8% fructose water, and the rats in intervention group were fed with water containing 8% fructose and 1% glycine. The body weight and systolic pressure were measured monthly. After 8 months, plasma glucose, plasma lipids, glucose tolerance and plasma endotoxin (LPS) were detected. Plasma insulin, pro-inflammatory cytokines in plasma and cerebral cortex were determined by ELISA, and HOMA-IR was also calculated. The molecules of insulin signaling pathway in cerebral cortex were determined by Western blotting. The cognitive functions of the rats were tested by Morris water maze. RESULTS: The weight gain in model group was increased from the 3rd month to the 6th month, and systolic pressure was increased after the 3rd month as compared with control group. Glycine significantly reduced the weight gain in the 4th month and the 6th month, and significantly reduced the systolic pressure from the 4th month to the 6th month. Meanwhile, glycine partly attenuated dyslipidemia and glucose intolerance, and lowered the levels of plasma LPS, plasma insulin, HOMA-IR and pro-inflammatory cytokines in plasma and cortex. Furthermore, glycine attenuated the abnormal expression of insulin signaling proteins and cognitive impairment. CONCLUSION: Long-term fructose diet induces the rats to peripheral and neuronal IR, which accompanies IETM and low-grade inflammation. Glycine attenuates IR and cognitive impairment by lowering IETM.     

Correlation between post-operation insulin resistance and intestinal barrier dysfunction in obstructive jaundice rats

AIM：To investigate the correlation between post-operation insulin resistance (IR) and intestinal barrier dysfunction in obstructive jaundice (OJ) rats. METHODS：The rat model of OJ was set up. The rats were randoml divided into control group (sham operation), OJ group, glucagon-like peptide 2 (GLP-2) group (challenged with GLP-2 by intraperitoneal injection) and insulin group (insulin subcutaneous injection). Peripheral blood was collected 1 d before operation and 2 h, 24 h, 48 h, 3 d and 7 d after operation. The IR index and the ratio of lactulose/mannitol (L/M) were determined. The concentration of serum resistin-like molecule (RELM) β was detected by ELISA. The relative mRNA level of RELMβ in terminal ileum enterocytes was measured by semi-quantitative RT-PCR. RESULTS：The IR index and the ratio of L/M in OJ group 3 d after operation were 10.1±1.8 and 0.66±0.08, respectively, which were higher than those at other time points (all P<0.05). The correlation coefficient between the changes of IR index and ratio of L/M was 0.86 (P<0.05). The IR index in GLP-2 group descended by 37.0% 7 d after operation (7.33±1.07 vs 4.62±0.53, P<0.05). The highest concentration of serum RELMβ was observed in OJ group 3 d after operation (0.69 μg/L±0.05 μg/L). The relative mRNA level of RELMβ in terminal ileum enterocytes was also increased obviously. The expression of RELMβ was obviously decreased in GLP-2 group and insulin group. CONCLUSION：There is closed relationship between post-operation insulin resistance and intestinal barrier dysfunction. The RELMβ is the point of intersection. Enterocytes are not only the source of post-operation insulin resistance but also the target organ.     

Role of insulin resistance in neurodegenerative diseases

Insulin resistance is a condition in which the cells fail to respond to the normal actions of insulin, acting as decreased glucose utilization, abnormal glucose tolerance and compensatory increased insulin concentration in the serum. Altered insulin-related indicator has been detected in neurodegenerative diseases. Recent studies indicate that insulin resistance is involved in the occurrence and development of neurodegenerative diseases, including Alzheimers disease, Parkinsons disease, Huntingtons disease, etc. This review summarizes the relationship between insulin resistance and neurodegenerative diseases.     

Influence of obesity on first-phase insulin secretion in individuals with different glucose tolerance

AIM: To explore the influence of obesity on the first-phase insulin secretion in the individuals with different glucose tolerance. METHODS: Thirty-eight subjects with normal glucose tolerance without family history of diabetes (normal control,NC), 32 subjects with normal glucose tolerance (NGT) who were the first-degree relatives of type 2 diabetic patients, 67 patients with impaired glucose regulation (IGR) and 35 newly-diagnosed type 2 diabetic patients (T2DM) were enrolled in the study. The patients in the 4 groups were further divided into 2 subgroups: overweight/obesity and normal weight subgroups. All subjects received oral glucose-insulin release test (OG-IRT) and intravenous glucose tolerance test (IVGTT). Acute insulin response at 3~5 min (AIR3-5) was used to reflect first-phase insulin secretion,and insulin sensitivity index (ISI) was used to reflect insulin sensitivity. The influence of obesity on the islet β-cell function and insulin sensitivity in the individuals with different glucose tolerance was observed. RESULTS: The level of AIR3-5 in NC overweight/obesity subgroup was significantly higher than that in normal weight subgroup (P<0.05), while there was no significant difference between other subgroups (P>0.05). No significant difference in the level of ISI between the patients of IGR in overweight/obesity subgroup and normal weight subgroup was observed, while in the other 3 overweight/obesity subgroups, ISI was lower than that in normal weight subgroups (P<0.05). ISI was negatively correlated with body mass index and waist circumference in all groups (P<0.05). ISI was also positively correlated with AIR3-5 in NC group and negatively correlated in the other 3 groups (P<0.05). CONCLUSION: The impact of obesity on insulin secretion is not the same in the subjects with different glucose tolerance. With the aggravation of insulin resistance, the first-phase insulin secretion in the subjects with normal glucose tolerance without family history of diabetes increases for compensation, while that in the normal glucose tolerance subjects who are the first-degree relatives of type 2 diabetic patients, the patients with impaired glucose regulation and the type 2 diabetic patients could not increase for compensation.     

Protective effect of chrysin on mice with insulin resistance

AIM: To explore the effects of chrysin on insulin resistance (IRe) in a mouse model. METHODS: Male C57 mice were randomly divided into control group, IRe group, low-dose chrysin group (IRe+chrysin-low) and high-dose chrysin group (IRe+chrysin-high). After 24 weeks, the body weight, liver index and fat mass in all mice were detected. The blood glucose, insulin level and HOMA-IR were measured to determine the changes of the insulin resistance in the animals. The oxidative stress (SOD, GSH-Px and MDA) was also measured. The mRNA expression of insulin signaling pathway molecules (IR, IRS1, IRS2, Glut2 and Glut4) and inflammatory factors (TNF-α, IL-1β, IL-6 and NF-κB) was analyzed by real-time PCR. The protein levels of IRS1 and p65, and their phosphorylation were detected by Western blot. RESULTS: After 24-week intervention, the indicators in IRe group were higher than those in control group, including body fat deposition, serum glucose, serum insulin, HOMA-IR and liver oxidative stress (P<0.01), indicating that the model of insulin resistance was successfully established. Low dose and high dose of chrysin decreased the body weight, serum glucose, serum insulin and HOMA-IR in the IRe mice (P<0.05). The liver oxidative stress was also reduced in both groups (P<0.05). However, no statistical difference of the indexes between IRe+chrysin-low group and IRe+chrysin-high group was observed. Chrysin upregulated the mRNA expression of IR, IRS1, IRS2, Glut2 and Glut4 (P<0.05), and down-regulated the mRNA expression of various inflammatory factors. The inhibitory effect of chrysin on the mRNA expression of NF-κB was observed (P<0.05), especially in high dose group (P<0.05). It was confirmed that the effect of chrysin on liver IRe was related with the increase in the p-IRS1 levels and decrease in the p-p65 levels by Western blot. CONCLUSION: Chrysin inhibits obesity, hyperglycemia and hyperinsulinemia, and relieves insulin resistance and oxidative stress, which might be closely related to the regulation of insulin signaling pathway and the inhibition of inflammatory factor expression.     

Effects of insulin and glucose on secretion of tissue-type plasminogen activator and its inhibitor-1 in hypoxic vascular endothelial cells

AIM: To study the effects of insulin and glucose on tissue-type plamingen activator (tPA) and its inhibitor-1 (PAI-1) secretion in cultured human endothelial cells. METHODS: Human endothelial cell line ECV-304 was cultured with glucose and/or insulin at different concentrations with or without hypoxic exposure. RESULTS: The tPA, PAI-1 secretion and ratio of tPA/PAI-1 increased in endothelial cells during hypoxia. Insulin and glucose increased the tPA and PAI-1 secretion in endothelial cells exposed to hypoxia, and increase in tPA/PAI-1 ratio was also observed at 4 h and 8 h. CONCLUSION: Hypoxia stimulates the release of tPA and PAI-1. Insulin and glucose also stimulate the tPA and PAI-1 secretion during hypoxia.     

Effect of insulin resistance on fatty liver in high-fat diet-fed mice

AIM: To study the influence of insulin resistance on fatty liver in the mice fed with high-fat diet (HFD).METHODS: Male 8-week-old C57BL/6J mice were randomly divided into HFD group (with 60% calories by high saturated fatty acid) and control group (with chow diet).The mice in both groups were fed for 12 weeks. The body weight, liver weight, serum triglyceride (TG) and total cholesterol (TC), and blood glucose and insulin levels were measured. Hyperinsulinemic euglycemic clamp experiment was applied to reflect insulin sensitivity. The lipid deposition in the liver was analyzed by HE staining, Sudan IV staining and measurement of liver fat content. The phosphorylation levels of IRS1 and Akt, and the protein levels of SREBP-1 and FAS were determined by Western blot to reflect the activities of insulin signaling and lipid synthesis.RESULTS: Compared with control group, the body weight and liver weight were significantly increased in HFD group. TG and TC contents in serum and liver tissues were remarkably increased in HFD group. High-fat diet induced insulin resistance, as evidenced by increased serum insulin levels, reduced glucose infusion rate and decreases in IRS1 and Akt phosphorylation levels. In livers of HFD group, HE staining showed that the cytoplasm of hepatocytes was filled with vacuoles. Sudan IV staining also displayed that many different sizes of red lipid drops existed in the hepatocytes, and the protein levels of SREBP-1 and FAS were significantly increased. In primary normal hepatocytes with exogenous oleic acid intervention for 48 h, the phosphorylation levels of IRS1 and Akt were reduced, and the protein expression of SREBP-1 and FAS was significantly increased in a dose-dependent manner.CONCLUSION: Feeding with HFD leads to insulin resistance, resulting in activation of lipid synthesis and accumulation of lipid deposition in the liver, thus inducing fatty liver.     

Effect of taurine on L-arginine/NO pathway in erythrocytes of rats of hypertension with insulin resistance induced by fructose

AIM and METHODS:The present study observed the change of L-arginine(L-Arg)/Nitric oxide(NO)pathway in ergthrocytes in hypertension with insulin resistance rat induced by fructose and the effect of taurine on L-Arg/NO pathway.RESULTS:Drinking 4%fructose, while inducing blood pressure, glucose and plasma insulin contents increase, obviously decreased the maximal velocity of L-Arg transport about 31%and 37%(P<0.01), more than that of control group in total and Y⁺ carrier, the NO synthase(NOS)activity, nitrite(NO₂^-)content and cyclic guanylate monophosphate(cGMP)level more than that of control group, but obviously enhanced Michaelis Constant(Km)about 35%and 30%(P<0.01)more than that of control group in total and Y⁺ carrier transport.The taurine treatment significantly counteracted the above changes.CONCLUSION:There exists a functional disturbance in L-Arg/NO system in the erythrocyte of hypertension rats with insulin resistance, but taurine can obviously enhanced the maximal velocity of L-Arg transport and NOS activity.Thus, it appears that taurinemay have vital value in the treatment of hypertension with insulin resistance.     

Research progress in regulation of glucose metabolism by osteocalcin

Osteocalcin (OCN) is a non-collagenous protein, which is synthesized and secreted by osteoblasts and closely associated with bone metabolism. Previously, blood circulation-derived OCN has been confirmed to promote β-cell proliferation, enhance insulin secretion, and improve insulin sensitivity by increasing the expression of adiponectin. Recent studies indicate that insulin signaling in the regulation of OCN activity mediated by osteoblasts is through the enterococcal surface protein (ESP) gene to increase the expression of OCN gene and enhance OCN activity by favoring bone resorption. Meanwhile, adiponectin may also behave as a kind of insulin secretagogue potentially. Intense researches on the specific mechanism concerning the effects of insulin signaling and adiponectin during the process of glucose homeostasis by OCN may provide new therapeutic targets for treating diabetes and its related complications.     

Effect of insulin on early myocardial oxidative stress in severely burnt rats

AIM：To investigate the effect of insulin on early myocardial oxidative stress in severely burnt rats. METHODS：Twenty-four Sprague-Dawley rats were randomly divided into three groups (8 rats in each group): control group (sham scald group), scald injury group and scald injury + insulin group. The rats in the latter two groups were subject to third-degree burn with 30% total burn surface area (TBSA) on the back, and then received intraperitoneal injection of normal saline (40 mL/kg) immediately. The rats in scald injury + insulin group were subcutaneously injected with insulin (1 U/kg), while those in scald injury group received subcutaneous injection of the same volume of normal saline. All rats were sacrificed 24 h after scald, and blood samples from abdominal aorta and myocardial tissues were taken. Blood glucose (BG) content, blood lactate dehydrogenase (LDH) and creatine kinase (CK) activity, and myocardial oxidative and antioxidative indexes, including malondialdehyde (MDA), xanthine oxidase (XO), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GPx), were detected by spectrophotometry. RESULTS：(1) Compared with control group, BG levels in scald injury group and scald injury + insulin group were significantly elevated (P<0.05). But BG in scald injury + insulin group was significantly lower than that in scald injury group (P<0.05). (2) Compared with control group, the activity of LDH and CK in scald injury group was significantly increased (P<0.05), while that in scald injury + insulin group was significantly lower than that in scald injury group (P<0.05). (3) Compared with control group, the MDA content and the XOD and MPO activity in scald injury group were significantly increased (P<0.05), while the activity of SO, CAT and GPx was significantly decreased (P<0.05). Compared with scald injury group, the MDA content and the XO and MPO activity in scald injury + insulin group were significantly reduced (P<0.05), while the activity of SOD, CAT and GPx was significantly elevated (P<0.05). CONCLUSION：Insulin intervention attenuates early myocardial oxidative stress in burnt rats and decreases the rise in myocardial enzyme activity, thus exerting a cardioprotective effect.     

The alteration of expression of iNOS mRNA and ecNOS mRNA in peripheral leukocytes from insulin resistance rats fed with fructose

AIM: To study the alteration of expression of iNOS mRNA and ecNOS mRNA in peripheral leukocytes of Wistar rats fed with fructose. METHODS: Wistar rats were randomly divided into the control group (n=10) and the fructose feeding group(n=10). The fructose feeding group drank12% fructose water for 6 months. The blood glucose, blood insulin, and the expression of iNOS mRNA and ecNOS mRNA in peripheral leukocytes of rats were determined. RESULTS: The levels of blood insulin (P<0.01) and the expression of ecNOS mRNA were higher in fructose feeding group than that in control group after1month. The level of blood insulin(P<0.01), the level of blood glucose (P<0.05), the expression of ecNOS mRNA and the iNOS mRNA were also higher in fructose feeding group than that in control group after 2 months. The levels of blood insulin and glucose, the expression of ecNOS mRNA and the iNOS mRNA were increased persistently during 3 to 6 months. CONCLUSIONS: These results indicate that fructose can increase the level, but reduce the sensitivity of insulin. It can also induce the expression of ecNOS mRNA firstly and the expression of iNOS mRNA secondly, the former can delay the formation of insulin resistance and the later can accelerate the formation of insulin resistance.     

Effect of GLP-1 on insulin resistance and PKCε in rats with nonalcoholic fatty liver disease induced by high fat diet

AIM: To observe the therapeutic effect of glucagon-like peptide 1 (GLP-1) analog on nonalcoholic fatty liver disease of rats and to investigate the underlying mechanism.METHODS: SD rats (n=21) were used to establish a nonalcoholic fatty liver disease model by feeding a high fat diet for 12 weeks, and other 11 rats were fed with a normal diet for 16 weeks. The model rats were randomly divided into 2 equal groups:one group was treated with glucagon-like peptide 1 analog (0.6 mg·kg^-1·d^-1) by intraperitoneal injection for 4 weeks, the other group using saline as a control. After treatment, fasting blood glucose, serum insulin, blood lipids, liver function and the pathological changes of the hepatic tissues were evaluated and the expression of PKCε at mRNA and protein levels in the liver tissues was detected by real-time PCR and Western blot, respectively.RESULTS: Compared with model group, the intervention of GLP-1 significantly reduced insulin resistance index (HOMA-IR), improved the liver function (P<0.05), decreased the liver index and blood lipids (P<0.05). HE staining showed obvious pathological changes of the hepatic tissues in model group, and the intervention of GLP-1 significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver. The expression of hepatic protein kinase Cε (PKCε) at mRNA and protein levels significantly decreased which were reversed by treating with GLP-1.CONCLUSION: GLP-1 shows good therapeutic effect on nonalcoholic fatty liver disease of rats, possibly by controlling lipid metabolism and reducing insulin resistance, which may be related to PKCε expression.     

Effects of insulin on cardiac fibroblast proliferation and cardiac myocyte hypertrophy

AIM:To study the effect of insulin on proliferation and hypertrophy of cardiac myocytes and its role in the induction of cardiac hypertrophy. METHODS:1. The neonatal rat cardiac myocytes and cardiac fibroblasts were cultured respectively and identified with light microscopy, electron microscopy and immunocytochemistry. 2. Cell proliferation was measured with cell number, metabolic activity and DNA synthesis (with WST-1, BrdU enzyme-linked immunosorbent assay ) and the percentage of S+G₂+M in cell cycle (by flow cytometry ). 3.Cell hypertrophy was evaluated by cell protein content (Coomassie Briliant Blue's method). RESULTS:1. The cultured cells showed the characteristic of cardiac myocytes and cardiac fibroblasts, respectively. 2. After being treated with insulin, the cell number, absorbance of BrdU incorporation and WST-1 cleavage products and the percentage of S+G₂+M of cardiac fibroblasts increased significantly (P＜0.01 orP＜0.05), while the above parameters of cardiac myocytes remained unchanged (P＞0.05). 3. Protein content of cardiac myocytes increased significantly in a dose-dependent manner (P＜0.01 orP＜0.05) in insulin treated groups (10^-10 mol/L-10^-7 mol/L). CONCLUSION:Insulin promoted cardiac fibroblast proliferation and increased myocytes protein content(induced myocyte hypertrophy)in vitroand may play an important role in pathogenesis of cardiac hypertrophyin vivo.     

Mechanism of hepatic insulin resistance induced by high-fat diet

AIM: To observed the relationship between oxidative stress and development of insulin resistance in hepatic tissues of Sprague dawley(SD) rats by analyzing reactive oxygen species(ROS) level and NADPH oxidase 3(NOX3) expression in livers. METHODS: Four-week-old male SD rats were fed with high-fat diet containing 20% fat and 20% sucrose for 12 weeks to induce insulin resistance. Plasma insulin level was detected by radioimmunoassay. The content of liver intracellular glycogen was measured using a glycogen assay kit. ROS generation in the liver tissues was assessed by dihydroethidium(DHE) fluorescence. The expression of NOX3 was determined by Western blotting.RESULTS: After 12 weeks of high-fat diet feeding, the content of blood glucose was increased but still maintained in normal level in the rats. However, the index of insulin sensitivity obviously decreased. Hepatic glycogen content in the rats fed with high-fat diet was significantly decreased, indicating that insulin resistance developed. Enhanced ROS production in hepatic tissues of the rats fed with high-fat diet was observed. Importantly, the expression of NOX3 in the liver was up-regulated in response to high-fat diet in vivo.CONCLUSION: High-fat diet feeding decreases insulin sensitivity, enhances ROS level and NOX3 expression, and reduces glycogen content in the livers.     

Protective effect on hepatic insulin resistance of Astragalus polysaccharide in the high fat-fed mice model

AIM: To investigate the effect and mechanism of Astragalus polysaccharide (APS) on the amelioration of hepatic insulin resistance in high fat-fed mouse model.METHODS: C57BL/6J mice (n=26) were divided into three groups randomly: C group (an animal model for control,n=10);IR group ( an animal model of insulin resistance,n=8) and IA group (an animal model in high-fat diet with APS treatment for12 weeks,700mg·kg^-1·d^-1,ig).High-fat diet was used to induce the formation of insulin resistant.The parameters and insulin sensitivity of the animals were observed.The pathological features of the liver were presented through microscope and TEM.The expression changes of hepatic GSK3β were measured by Western blotting.RESULTS: In this study,the fat-fed mouse model of insulin resistance was established successfully.The mice in IA group responded to the 12-week APS therapy with a significant decrease in the level of blood glucose,plasma insulin,body weight,hepatic TG/FFA and improved glucose tolerance compared with those in IR group.In addition,the expression and the activity of GSK3β were lower in IA group (vs IR group，P<0.05).We also found the hepatic steatosis could be significantly alleviated with APS therapy.CONCLUSION: These results indicate that APS prevents the occurrence of insulin resistance and the hepatic steatosis induced by high-fat diet,at least in part by inhibiting the expression and activity of the hepatic GSK3β.     

Strategies for preventing and curing insulin resistance in lipid-overloaded cardiac myocytes

Insulin resistance is a central pathological mechanism of type 2 diabetes mellitus. Diabetic cardiomyopathy and heart failure are frequent co-morbid conditions in type 2 diabetic patients. Long-chain fatty acids (LCFAs) are the major energy source for the heart to sustain contractile activity, and the diabetic heart becomes almost entirely dependent on LCFAs for energy production. Elevated intracellular levels and prolonged accumulation of LCFA metabolites worsen the state of insulin resistance, and further induce diabetic cardiomyopathy and heart failure. It is indicated that sarcolemmal fatty acid uptake and mitochondrial β-oxidation are the rate-limiting steps in cardiac LCFA flux and utilization. Therefore, the inhibitions of carnitine palmitoyltransferase (CPT-I), β-oxidation enzymes and CD36/plasma membrane fatty acid-binding protein (FABPpm) translocation are the preferable strategies of limiting LCFA entry and LCFA metabolite accumulation, thus regressing cardiac insulin resistance, and eventually preventing diabetic heart failure.     

Association of serum soluble E-selectin concentrations with insulin resistance in essential hypertension patients

AIM: To investigate the relationship between serum soluble E-selectin (sE-selectin) and insulin resistance, serum uric acid, serum lipid in essential hypertension patients. METHODS: Fasting serum sE-selectin concentration, plasma glucose, serum insulin, serum uric acid, total cholesterol, triglycerides, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol were determined in 186 patients with essential hypertension (75 males, 111 females). Homeostasis model assessment was applied to assess the status of insulin resistance (HOMA-IR). RESULTS: Based on the HOMA-IR, the essential hypertension patients were divided into insulin-sensitive individuals (IS) and insulin resistant subjects (IR). The serum sE-selectin concentration was significantly higher in male group [(50.1±17.8)g/L]than in female group [(40.6±16.6)g/L](P<0.01). No difference between IR group [(51.6±16.8)g/L]and IS group [(48.5±18.8)g/L] in male, and significantly higher in IR group [(45.1±18.0)g/L]than in IS group [(36.0±13.7)g/L](P<0.01) in female were observed. A stepwise multiple linear regression analysis showed that HOMA-IR was an independent predictor of serum sE-selectin concentrations in female group and not in male group, and both serum uric acid and serum lipid were not independent predictors of serum sE-selectin concentrations. CONCLUSION: Serum sE-selectin concentrations were directly related to insulin resistance in females with essential hypertension and not in males with essential hypertension. Both serum uric acid and serum lipid were not directly related to serum sE-selectin concentrations.     

Oxymatrine ameliorates high fat-induced insulin resistance in ApoE-/- mice

ATM: To investigate the effect of oxymatrine (OXY) on high fat-induced insulin resistance in mice, and to investigate the mechanism. METHODS: ApoE^-/-mice with high-fat diet for 16 weeks were divided into insulin resistance group, and OXY groups at concentrations of 25, 50 and 100 mg/kg. C57BL/6J mice served as normal control group. The mice in OXY groups were gavaged with OXY for 8 weeks. Glucose tolerance test in the mice was performed. Fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), fatty acid (FFA) and fasting insulin (FINS) in the plasma were measured. The mRNA expression of insulin receptor (INSR), insulin receptor substrate-2 (IRS-2), glucose transporter 2 (GLUT2) in the liver tissues was examined by RT-qPCR. The protein levels of GLUT2, INSR, IRS-2, p-INSR, p-IRS-2, PI3K, p-PI3K, serine/threonine protein kinase (AKT) and p-AKT were examined by Western blot.RESULTS: OXY reduced the levels of FBG, TC, TG, FFA and FINS, and attenuated insulin resistance. Compared with insulin resistance group, the mRNA expression of INSR, IRS-2 and GLUT2 significantly increased in OXY groups (P<0.05). The protein levels of p-INSR/INSR, p-IRS-2/IRS-2, p-PI3K/PI3K, p-AKT/AKT and GLUT2 also increased in OXY groups (P<0.05).CONCLUSION: OXY ameliorates high fat-induced insulin resistance in mice via PI3K/AKT pathway.