Changes of the first-phase insulin secretion in first-degree relatives of type 2 diabetic subjects with different glucose-tolerance

AIM: To investigate the role of the insulin secretion as well as insulin sensitivity in the onset and development of the type 2 diabetes mellitus (T2DM). METHODS: This study included 38 normal glucose tolerance(NGT) subjects without family history of diabetes, 32 NGT and 36 impaired glucose tolerance(IGT) subjects who were the first-degree relatives of type 2 diabetes, and 35 newly-diagnosed type 2 diabetic patients.β cell function and insulin sensitivity were examined by using oral glucose-insulin release test (OG-IRT) with SIM reflecting insulin sensitivity and intravenous glucose tolerance test (IVGTT) with AIR3-5 reflecting the first-phase insulin secretion function. AIR3-5 was calculated as the average incremental plasma insulin concentration from the third to the fifth minute after the glucose bolus. AIR3-5 and SIM were compared among the four groups. RESULTS: From NGT, IGT to type 2 diabetes,there was a decreasing tendency of the level of AIR3-5 and SIM with NGT the highest, IGT the medium and T2DM the lowest. The level of the AIR3-5 in the subjects of NGT who were first-degree relatives of type 2 diabetes were lower than those of NGT without family history of diabetes（P<0.01）, while there was no significant difference in the SIM level between the two groups（P>0.05）. CONCLUSION: Insulin secretion dysfunction may be the primary factor in the onset of type 2 diabetes. Along with the developing of IGT and type 2 diabetes, the insulin secretion and sensitivity decrease.     

Effect of L-glutamine on obesity and insulin resistance in high-fat diet-induced C57BL/6J mice

AIM:To explore the effect of L-glutamine (Gln) on obesity and insulin resistance in high-fat diet(HFD)-induced C57BL/6J mice. METHODS:Male C57BL/6J mice (n=60) were randomly divided into normal control (NC) group, HFD group, HFD+L-alanine (Ala) group and HFD+Gln group. Each group had 15 mice. The body weight of the mice was recorded weekly. Fasting blood glucose (FBG) of the mice was tested after 12-h fasting only with water-drinking at the end of the 16th week. The mice were sacrificed and epididymal fat pad was measured. The levels of insulin (INS), leptin (LEP), adiponectin (APN) and glucagon-like peptide-1 (GLP-1) were measured by ELISA. The insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated. RESULTS:Compared with NC group, the body weight, epididymal fat pad weight, and the levels of FBG, INS, IRI and LEP increased significantly in HFD group (P<0.05), while the levels of ISI and APN decreased significantly (P<0.05). Compared with HFD group, the body weight, and the levels of FBG, IRI and LEP decreased significantly in HFD+Gln group (P<0.05), while the levels of ISI and APN increased significantly (P<0.05). No significant difference of serum GLP-1 levels the four groups was observed. CONCLUSION:L-glutamine reduces the body weight and attenuates the insulin resistance of HFD-induced mice.     

Serum levels of inflammatory factors and adiponectin in type 2 diabetic retinopathy patients

AIM: To investigate the serum levels of inflammatory factors and adiponectin in type 2 diabetic retinopathy (DR) patients.METHODS: One hundred and ten cases of type 2 diabetic patients were divided into 3 groups: no diabetic retinopathy group (DM, n=35), non-proliferative diabetic retinopathy group (NPDR, n=45), and proliferative diabetic retinopathy group (PDR, n=30). Other 40 normal persons served as controls (NC group). The physical examinated was performed for each patient. Serum levels of fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), 2 h postprandial plasma glucose (2hPG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), adiponectin, intercellular adhesion molecule-1(ICAM-1), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) were measured. Insulin resistance index (HOMA-IR) was also calculated.RESULTS: The systolic blood pressure, body-mass index, waist-hip ratio, serum levels of TG, LDL-C, FPG, 2hPG, HbA1c, ICAM-1, TNF-α, hs-CRP and HOMA-IR were significantly higher in DM group, NPDR group and PDR group than those in NC group (P<0.05). The systolic blood pressure, serum levels of ICAM-1, TNF-α, hs-CRP and HOMA-IR were higher in NPDR group and PDR group than those in DM group (P<0.05). The serum concentration of adiponectin was lower in DM group, NPDR group and PDR group than that in NC group (P<0.05), and that was also lower in NPDR group and PDR group than that in DM group (P<0.05). The negative correlations between adiponectin and ICAM-1 (r=-0.735,P<0.01), TNF-α (r=-0.781,P<0.01), hs-CRP (r=-0.768, P<0.01) or HOMA-IR (r=-0.752, P<0.01) were observed. The relationships between HOMA-IR and ICAM-1 (r=0.857,P<0.01), TNF-α (r=-0.906, P<0.01) or hs-CRP (r=-0.888,P<0.01) were positive.CONCLUSION: The results suggest that inflammatory refactors and adiponectin play important roles in the pathophysiology and progression of DR. The protective effects of adiponectin on DR may be related with its anti-inflammatory reactions to improve insulin resistant.     

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.     

Effect of blood glucose and insulin on serum free fatty acid level after gluconse loading in essential hypertension patients

AIM: To investigate the effects of internal change of serum insulin and plasma glucose levels on serum free fatty acid (FFA) concentrations after glucose loading. METHODS: Serum insulin, plasma glucose and FFA concentrations were measured simultaneously in 234 essential hypertension patients who were undergoing oral glucose tolerance test (OGTT)[including 20 cases with 2 type diabetes mellitus(DM),74 impaired glucose tolerance(IGT),140normal glucose tolerance(NGT);98 males,136 females]. RESULTS: Fasting serum FFA concentration (μmol/L) in DM (1 048.47±481.6) was higher than that in IGT (760.1±332.1) (P＜0.05) and in NGT (725.8±353.9) (P＜0.05). Compared with the NGT group, the glucose curve was elevated and the insulin releasing curve was characterized by a low response and a delayed peak in DM group. As for the FFA releasing curve, three groups showed a significantly decreasing trend, which was more evident in DM group. Serum FFA levels at 30 min, 60 min and 120 min after glucose ingestion were not significantly different between the three groups. CONCLUSIONS: Easting serum FFA levels were elevated in DM group. The absolute deficiency of insulin secretion decreased rather increased the difference of FFA level difference between DM group and IGT group, NGT group during OGTT. These results suggest the level of glucose utilization may have an important effect on serum FFA concentration.     

Correlation among plasma leptin,resistin an type 2 diabetes mellitus

AIM：To assess the association of resistin,obesity,serum lipid levels and insulin resistance with plasma leptin.METHODS：The concentrations of fasting serum glucose,insulin,lipid profiles,plasma resistin and leptin were assayed in 80 cases (including 37 controls with normal glucose tolerance and 43 patients with type 2 diabetes mellitus).RESULTS：Fasting plasma leptin level was positively correlated with sex,body mass index (BMI),waist circumference (WC),waist-hip ratio and fasting serum insulin (F Ins) （P<0.01）.Fasting plasma leptin level was negatively correlated with insulin sensitivity index (r=-0.373,P<0.01).There was no correlation between the concentrations of plasma leptin and FPG,TG,TC and resistin （P>0.05）.CONCLUSION：Fasting plasma leptin level is positively correlated with obesity and insulin resistance,not resistin.Leptin may play a role in the pathogenesis of type 2 diabetes mellitus.     

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.     

Effect of micronised fenofibrate on lipotoxicity and insulin sensitivity in spontaneously hypertensive rats treated with high-fat diet

AIM: To observe the effect of micronised fenofibrate (lipanthyl) on lipotoxicity and insulin sensitivity (IS) in spontaneously hypertensive rats (SHR) with high-fat diet.METHODS: Twenty-seven SHR were randomly divided into three groups: normal chow group (n=9), high-fat diet group (n=9) and micronised fenofibrate treatment group (n=9). Micronised fenofibrate 100 mg·kg-1·d-1 was given orally to SHR, which diet on high-fat diet for three months. Intramuscular lipids were observed and lipids accumulation index (LAI) was calculated. Nonesterified fatty acid, glucose and insulin were determined in all rats.RESULTS: (1) Compared to SHR in normal chow diet group, body weight and the level of serum TG and TC increased significantly and the level of HDL-C decreased significantly in SHR fed with high-fat diet (P<0.05). Micronised fenofibrate significantly decreased systolic blood pressure, body weight, the level of serum TG and TC, increased the level HDL-C (P<0.05). (2) Fasted blood glucose, free fatty acid (FFA), GLU-AUC obviously increased in high-fat diet group compared with normal chow diet group. Insulin sensitivity index (ISI) in high-fat diet group was much lower than that in normal chow diet group (0.0038±0.0007 vs 0.0053±0.0013, P<0.05). No difference was found between fenofibrate-treated group and normal chow diet group. (3) There were more lipid drops in intramuscular cells of SHR treated with high-fat diet than those in fenofibrate-treated group and normal chow diet group (LAI: 6.42±0.59 vs 3.32±0.77 and 1.98±0.97, P<0.05). After covariance analysis, the results above-mentioned also made sense (F=10.46, P<0.05). (4) Inverse association was found between LAI and ISI (r=-0.58, P<0.05). Positive correlations were found between LAI and TG, FFA, body weight.CONCLUSION: In addition to regulating lipid, micronised fenofibrate may reduce BP, body weight, FFA, lipid accumulation in intramuscular cells and improve insulin sensitivity of SHR treated with high-fat diet.     

Insulin protects endothelial progenitor cells against functional damage caused by high glucose

AIM: To investigate the impact of various levels of glucose on endothelial progenitor cells (EPCs) proliferation, senescence, and nitric oxide (NO) secretion,and the effect of insulin under high glucose conditions.METHODS: Mononuclear cells were collected from rat bone marrow by density gradient centrifugation, cultured with medium 199, and identified to be EPCs at 7th day by flk-1 and AC133 double staining. EPCss were harvested and incubated with glucose (5, 10, 20, 40 mmol/L) or insulin (0.1, 1, 10, 100 nmol/L) under high glucose conditions for 24 h or 7 days. Proliferative capacity, senescence level and NO secretion (after 24 h of incubation) were subsequently determined.RESULTS: High glucose (40 mmol/L) markedly inhibited EPCs proliferation, accelerated EPCs senescence, and decreased NO production (all P<0.05). Compared with high glucose (40 mmol/L) group, insulin intervention promoted EPCs proliferation, inhibited EPCs senescence (prominent at 1 nmol/L, P<0.05), and enhanced NO secretion (prominent at 10 nmol/L, P<0.05).CONCLUSION: High glucose harms EPCs proliferation and function, while insulin alleviates this jeopardy, indicating the protective role of insulin for the cardiovascular system.     

Effect of blood glucose control on expression of Smad7 and renal fibrosis in diabetic rats

AIM： To verify the hypothesis that treatment with insulin to control the blood glucose (BG) may relieve or slow down the development of diabetic nephropathy (DN) in diabetic rats by increasing the expression of Smad7. METHODS：The diabetic rat model was established by tail-vein injection of streptozotocin. Sixteen rats were divided into 2 groups. Eight of these animals in diabetes mellitus (DM) group had no treatment. The remaining eight of them in insulin treatment (INS) group were injected with insulin. After 13 weeks, the rats in INS group were given individual treatment with insulin to let the blood glucose level keep within 4 to 7 mmol/L. Meanwhile, 8 rats were used for normal control (NC group). After 16 weeks, the rats were sacrificed to detect the relevant biochemical parameters, and to observe the histophathological changes of the kidney and pancreas. In addition, immunohistochemical staining and Western blotting were employed to detect the protein expression of transforming growth factor β1 (TGF-β1), Smad ubiquitin regulatory factor 2 (Smurf2), Smad7, E-cadherin, α-sooth muscle actin (α-SMA), fibronectin (FN) and collagen I. RESULTS：Compared with NC group, the body weight was significantly reduced in DM group, whereas the body weight in INS group increased gradually. Compared with NC group, the levels of 24 h urine protein (24 h UP), BG and triglyceride (TG) were remarkably increased in DM group. Pathological detection on pancreas indicated that the islet was destroyed. The levels of TGF-β1, Smurf2, α-SMA, FN and collagenⅠ in the kidneys were increased in DM group, and the expression of Smad7 and E-cadherin, which were mainly located in renal tubular epithelial cells, was significantly reduced. Compared with DM group, the levels of 24 h UP and BG were significantly reduced in INS group, and the alleviated renal fibrosis was observed under light microscope. In addition, the protein levels of TGF-β1, Smurf2, α-SMA, FN and collagenⅠ in INS group were decreased compared with DM group, and the expression of Smad7 and E-cadherin was increased significantly. CONCLUSION：Target glucose control with insulin treatment restores the protein expression of Smad7 in the kidney of diabetic rats, reduces the accumulation of extracellular matrix and slows down DN progress. The decrease in TGF-β1 and Smurf2 expression, and the attenuation of Smad7 ubiquitination in renal tissues are the crucial parts in this process.     

The interrelationships between serum HDL subpopulations and triacyglycerol

AIM: To Study the influence of plasma TG level on the contents of serum HDL subpopulations. METHODS: Classified by the contents of serum TG, the serum level of HDL subpopulations in 106 normal TC and 183 high TC subjects were analyzed by two-dimensional gel electrophoresis coupled with immunodection method. RESULTS: The apo-AⅠcontents of per-β1-HDL, HDL3c, HDL3b and HDL3a were higher in a certain extent in TC high subjects vs corresponding TC desirable subjects. The apo-AⅠ contents of per-β1-HDL （in borer-line high TG subgroup） and HDL3b （in very high TG subgroup） were significantly higher (P<0.05 or P<0.01), while the apo-AⅠ contents of HDL2b and HDL2a were all lower in TC high subjects vs corresponding TC normal subjects. With the increase in plasma TG levels, the apoA-Ⅰ content of pre-β1-HDL increased, and it was significantly higher (P<0.05 or P<0.01) in borderline-high TG(except TC desirable subjects), high TG and very high TG subgroups vs corresponding normal TG subgroup. Contents of HDL3b and HDL3a had the same tendency, and in TC high subjects contents of HDL3b (in very high TG subgroup) and HDL3a (in every subgroups, in which levels of TG were higher) were significantly higher (P＜0.05 and P＜0.01） than in normal TG subgroup. On contrast, the apoA-Ⅰcontents of HDL2b and HDL2a following with the increase of plasma TG levels tended to become lower. Contents of HDL2b were significantly lower (P<0.05) in high TG subgroup and very high TG subgroup vs corresponding normal TG subgroup, and in TC high subjects contents of HDL2a were significantly lower (P<0.05) in very high TG subgroups vs normal TG subgroup. CONCLUSION: Our data show the general shift toward smaller size of HDL particle size with the increase in TC and TG levels. Contents of TC and TG are very important to contents of HDL subclasses.     

Effects of TNF-α-mediated insulin resistance on INSIG2 and SCAP expressions in vivo

AIM: To investigate the effects of TNF-α induced insulin resistance (IR) on INSIG1, INSIG2, SCAP and SREBP expressions in mice. METHODS: Male C57BL/6J mice were randomly divided into 4 groups. The mice were given an intraperitoneal injection of TNF-α (6 μg·kg-1·d-1; 3 μg·kg-1·d-1 and 1 μg·kg-1·d-1) and saline (NC group) twice daily for 7 d. The insulin sensitivity and glucose metabolism in awaken mice were evaluated by intravenous glucose tolerance test (IVGTT). The mRNA expression and protein levels of gene were measured by RT-PCR and Western blotting. RESULTS: After TNF-α treatment, fasting blood glucose (FBG), plasma insulin and free fatty acids (FFA) were significantly elevated in TNF-α (6 μg·kg-1·d-1) group compared to NC, TNF-α (1 μg·kg-1·d-1) and TNF-α (3 μg·kg-1·d-1) groups (P<0.01 and P<0.05, respectively). There was a lower glucose tolerance in TNF-α (6 μg·kg-1·d-1) group than that in other three groups during IVGTT. In TNF-α (6 μg·kg-1·d-1) group, the insulin release of glucose-stimulation was higher than that in NC and TNF-α (1 μg·kg-1·d-1) groups (P<0.01 and P<0.05). The INSIG2 mRNA expression of adipose tissues in TNF-α (6 μg·kg-1·d-1) group was significantly increased compared with NC group (P<0.01), and INSIG2 protein levels were also increased (P<0.05). In TNF-α treatment mice, SCAP mRNA level in adipose tissues was significantly up-regulated than that in the controls (P<0.05). The mRNA expressions of INSIG1 and SREBP1 in two groups were not significantly changed (P>0.05). CONCLUSION: In TNF-α induced insulin resistance, INSIG2 and SCAP may be involved in the pathways of lipid metabolism.     

Relationship between levels of plasma endothelin-1/serum nitric oxide and hearing impairment in type 2 diabetes

AIM: To evaluate the relationship between endothelin-1 (ET-1)/nitric oxide (NO) and hearing impairment in type 2 diabetes mellitus (DM).METHODS: Eighty-eight type 2 diabetic patients with no signs of microangiopathy (retinopathy and nephropathy) or peripheral neuropathy, and 53 healthy subjects in the same period were enrolled in this study. Auditory function was evaluated using pure tone audiometry. Totally,type 2 DM group (n=88) and normal control group (NC, n=53) were divided into subgroups based on the presence and absence of hearing impairment. The concentration of plasma ET-1 was detected by radioimmunoassay. The concentration of serum NO was measured by the method of nitric acid reductase.RESULTS: Significantly increased plasma ET-1 and decreased serum NO were observed in diabetic patients with hearing impairment compared with those in diabetic patients without hearing impairment. The results of multivariate logistic regression analysis showed that hearing impairment in type 2 DM group was significantly associated with elevated level of HbA1c (OR＝4.525, P<0.05), LDL-C (OR=2.381,P<0.05) and plasma ET-1 (OR＝6.207,P<0.01). Besides, elevated serum level of NO (OR＝0.862, P<0.05) was associated with lower risk of hearing impairment in diabetics.CONCLUSION: Hearing impairment may happen earlier than other complications in diabetic patients. In addition to hyperglycemia and hyperlipemia, high level of ET-1 and low levels of NO might contribute to hearing impairment in diabetic patients.     

Hypolipemic and hypoglycemic effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats

AIM: To investigate the effects of total triterpenoids from Psidium guajava leaves (TTPGL) on blood glucose and lipids in type 2 diabetic rats. METHODS: The diabetic rats were induced by intraperitoneal injection of streptozotocin at dose of 35 mg/kg and feeding with high-fat diet. The animals were divided into 5 groups: diabetic model control group (model), TTPGL treatment groups (with the doses of 60, 120 and 240 mg/kg, respectively) and rosiglitazone treatment group (3 mg/kg). Another 12 normal SD rats were used as the normal controls. The rats received daily treatment for 6 weeks, and then the levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TCH), free fatty acid (FFA), glycosylated hemoglobin (GHb) and glycosylated serum proteins (GSP) were measured. The protein expression of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissues was detected by Western blotting. RESULTS: Compared with normal control group, the levels of FBG, GHb and blood lipids were increased in type 2 diabetic rats. The FINS, insulin sensitivity index, and the protein expression of PPARγ in adipose tissues were decreased. Compared with model group, the levels of FBG and GSP were decreased,and the FINS, insulin sensitivity index, and the protein expression of PPARγ in adipose tissues significantly increased in TTPGL treatment groups (with the doses of 120 and 240 mg/kg). The levels of serum TG,TCH and FFA were significantly lower in TTPGL treatment groups (P<0.01 or P<0.05) as compared with the model controls. CONCLUSION: TTPGL decreases the levels of blood glucose and lipids in diabetic rats. TTPGL also increases serum insulin level and improves insulin sensitivity. The action mechanism of TTPGL may be related to the increase in the protein expression of PPARγ.     

Role of asiatic acid in treatment of insulin resistance in mouse adipocytes

AIM：To investigate the effects of asiatic acid, one of triterpenoids from Psidium guajava leaves, on the proliferation and differentiation of 3T3-L1 preadipocytes, and glucose and lipid metabolism of insulin-resistant adipocytes. METHODS：The proliferation of 3T3-L1 preadipocytes was tested by MTT assay, and the accumulation of lipid droplets in differentiated preadipocytes was measured by oil red O staining. The insulin-resistant cell model was established by exposure of the cells to dexamethasone. The cellular glucose uptake was determined by glucose oxidase-peroxidase assay. The free fat acid (FFA) concentration was detected by colorimetric method. Secreted adiponectin were measured by ELISA. The protein levels of peroxisome proliferator-activated receptor γ (PPARγ) and protein tyrosine phosphatase 1B (PTP1B) in insulin-resistant adipocytes were analyzed by Western blotting. RESULTS：Compared with medium group, asiatic acid increased the proliferation of 3T3-L1 preadipocytes and inhibited their differentiation at a concentration range of 10~100 μmol/L (P<0.05 or P<0.01). At concentrations of 30 μmol/L and 100 μmol/L, asiatic acid enhanced cellular glucose uptake in the insulin-resistant adipocytes both in basic and insulin-stimulation states. Asiatic acid decreased FFA production (P<0.05), and down-regulated the protein expression of PTP1B (P<0.05, or P<0.01). However, no effect on the secretion of adiponectin and the protein expression of PPARγ was observed (P>0.05). CONCLUSION：Asiatic acid enhances glucose uptake and inhibits FFA production in insulin-resistant adipocytes via down-regulating the protein expression of PTP1B, all of which play the roles of increasing insulin signaling sensitivity to improve insulin resistance.     

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.     

Serum levels of visfatin and tumor necrosis factor-alpha in patients with pre-eclampsia and their relationship with insulin resistance

AIM: To explore the serum levels of visfatin (VF) and tumor necrosis factor-alpha (TNF-α) in the patients with pre-eclampsia (PE) and their correlation with insulin resistance (IR). METHODS: The severe PE patients (n=30), mild PE patients (n=30) and normal pregnant women (n=40) were selected according to the classification standard of PE. The serum levels of VF and TNF-α were measured by ELISA. Fasting plasma glucose (FPG) and fasting insulin (FIns) were detected by glucose oxidase method and radioimmunoassay, respectively. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by an automatic biochemical analyzer. According to calculating the mean arterial pressure (MAP), body mass index (BMI) and homeostatic model assessment for insulin resistance index (HOMA-IR), the correlation between IR and the levels of serum VF as well as TNF-α were analyzed.RESULTS: The levels of VF and TNF-α in severe PE group and mild PE group were significantly lower than those in normal pregnancy group (P<0.05). In addition, the levels of VF and TNF-α in severe PE group were lower than those in mild PE group (P<0.05). Linear correlation analysis showed that serum VF was positively correlated with TNF-α and HDL-C (P<0.05), and negatively with MAP and FIns (P<0.05). The serum TNF-α was positively correlated with HDL-C (P<0.05), and negatively with BMI, TG, MAP and FIns (P<0.05). Multiple stepwise regression analysis showed that FBG, FIns and HOMA-IR were relative independent factors of serum VF and TNF-α (P<0.05).CONCLUSION: Serum levels of VF and TNF-α are closely related to IR.