Objective To investigate the effect of HIV-1 protease inhibitor saquinavir on insulin signaling and β-cell function in rat INS-1 cells. Methods INS-1 cells were preincubated with 0 or 10 μmol/L saquinavir for 48 h, stimulated with 100 nmol/L insulin for 2 min or 20 mmol/L glucose for 30 min. Insulin signaling parameters were analyzed by immunoprecipitation and Western blot on cell lysates. Insulin concentrations in the supernatant were measured by ELISA, and standardized by cellular DNA contents. Cell count with trypan blue stain and MTT test were determined to evaluate the effect of saquinavir on cell viability. Results Treatment with saquinavir for 48 h significantly decreased insulin-stimulated phosphorylation of IRS-1, IRS-2 and Thr~(308)-phosphorylation of Akt in INS-1 cells by 60%, 66% and 55%, decreased the rate of basal insulin secretion and glucose-stimulated insulin release by 39% and 49% compared with control cells, respectively. Conclusions Treatment with saquinavir impairs insulin signal transmission in pancreatic β cells and results in insulin resistance in β cells. This effect might influence the function of β cells.

Objective To investigate the effects of mTOR/S6K1 signaling pathway on the development of insulin resistantce. Methods 20 male C57BL/6 mice were divided into normal diet group (NC) and high fat diet group (HF).HF mice were fed with high fat diet for 14 weeks and insulin resistance was confirmed in all mice. We observed the morphology of pancreatic islet by HE staining. Serum insulin concentration was also evaluated by ELISA. Northern blot, Western blot and immunofluorescence were performed to detect mTOR and S6K1 mRNA and protein expression in skeletal muscle. Results As compared with NC group,HF group showed that the body weight and fasting serum insulin level were increased by 21.99%(P＜0.05) and 181.82%(P＜0.01) respectively;the area of pancreatic islet was significantly increased;glucose tolerance was impaired;expressions of mTOR mRNA (125.61±10.43 vs 100.00, P＜0.05) and protein (137.41±7.86 vs 100.00, P＜0.01) were significantly increased. And we also found an significant increase in total S6K1 mRNA (154.98±16.26 vs 100.00, P＜0.01) and protein (137.36±3.08 vs 100.00,P＜0.01) as well as pS6K1 protein (390.15±69.62 vs 50.59±16.65,P＜0.01)expression in HF group as compared with NC group.Conclusions mTOR/S6K1 signaling pathway plays an important role in the development of higt fat diet induced insulin resistance.

Objective To determine the causative organisms and antimicrobial susceptibility of community- and hospital-acquired pneumonia (CAP and HAP) in type 2 diabetes in Fujian Provincial Hospital. Methods The data of becteria spectrum and their drug susceptibility in patients with type 2 diabetes complicated by pulmonary infection were retrospectively analyzed in January 1995 to October 2006. Results The isolated bacteria of sputum culture of 494 cases included 73 gram-positive cocci(16.7%),139 gram negative bacilli(31.9%)and 224 fungus(51.4%).G+ cocci mainly included staphylococci,G-bacilli mainly included Klebsiella pneumoniae,Bowman immovability bacillus and Pseudomonas aeruginosa.In both CAP and HAP,fungus and G- bacilli were the dominant pathogens.The pathogenic bacteria were resistant to multi-antibiotics,and the resistant rates from HAP patients was higher than those from CAP. Of the bacterial strains isolated from blood culture,G-bacilli constituted 87.5%. Conclusions Fungus and G-bacilli were the dominant pathogens.Phlegm culture and drug sensitive test are helpful for reasonable use of antibiotics for patients with type 2 diabetes complicated by pulmonary infection in clinical practice.

Objective To discuss the significance and alteration of heart rate turbulence (HRT) of diabetics with ventricular premature beats of coronary heart disease (CHD). Methods 107 patients were chosen and divided into DM group(n=30), CHD group (n=32)and normal group(n=45).The turbulence onset(TO)and turbulence slope(TS) were calculated and analyzed. Results For the diabetics with ventricular premature beats, TO value was higher and TS value was lower than the normal group(all P<0.05).The value of TO and TS of the diabetics with ventricular premature beats were similar to those of CHD(P>0.05). Conclusions HRT can be used to estimate the integrality and stability of cardiac autonomic nerve function for the diabetics and it is an important factor for diagnosis.

Objective To investigate the variance of daily glucose profiles at different stages of glucose metabolism so as to instruct the development of rational programs of treatment. Methods The CGMS(continuous glucose monitoring sysytem)data of NGT(nomal glucose tolerance),IFG(impaired fasting glucose), IGT(impaired glucose tolerance),IFG+IGT and newly diagnosed T2DM(type 2 diabetes mellitus)were analyzed. Results There was no significant difference between NGT,IFG and IGT in the level of glucose and the degree of glycemic excursion(P>0.05).The level of glucose and the degree of glycemic excursion in IFG plus IGT were significantly higher than those in NGT, IFG and IGT(P<0.05).There was no significant difference between IFG plus IGT and T2DM in the degree of glycemic excursion(P>0.05).The level of glucose in T2DM was significantly higher than that of other groups(P<0.05). Conclusions With the aggravation of abnormality of glucose metabolism,the level of glucose becomes higher and the degree of glycemic excursion becomes more serious.Early intervention is suggested on the stage of IFG plus IGT.

Objective To establish the microtiter plate radiobinding assay (RBA) of IA-2A and to evaluate its clinical application. Methods The purified ~(35)S - IA-2 was incubated with sera for 24 hours on a 96-well V-shaped bottom plate, and then transferred to the Millipore plate coated with protein A, and counted with liquid scintillation and luminescence counters after washing. The IA-2A levels were detected in 162 patients with type 1 diabetes(T1DM),210 patients with newly diagnosed type 2 diabetes(T2DM) and 224 healthy controls to evaluate clinical application of IA-2A RBA. Results 1. The intra-coefficient of variation (CV) of the assay was 4.1%～10.0%, and the inter CV was 5.7%～12.8%. 2. The results from DASP 2005 showed that the sensitivity and specificity of the assay were 72% and 98%. The results of IA-2A from two methods of RBA and classical radioligand assay(RLA) were significantly correlated (r=0.962,P＜0.001) with a consistency of 96.5%. 3. When compared with the healthy controls, T1DM patients had higher positivity for IA-2A (22.8% vs 0.89%, χ~2=49.9,P＜0.001), but no significant difference was found in T2DM patients(2.4% vs 0.89%, χ~2=1.5,P＞0.05). 4. The consistency rate of IA-2A measurement was 100% between RBA using finger tip blood and RLA using venous blood (r=0.977,P＜0.001). Conclusions The microtiter plate RBA of IA-2A using finger tip blood has high sensitivity, specificity and reproducibility, and possesses a good clinical value.

Objective To investigate the value and limitations of ultrasound determination-evaluated brachial artery endothelial function in elderly diabetic patients. Methods High-resolution two-dimensional ultrasound was used to determine brachial artery(BA) flow-mediated vasodilation(FMD) during reactive hyperemia. Endothelial function was evaluated by FMD in 67 elderly patients with type 2 diabetes. Results In diabetes versus normal control group,the BA diameter and flow velocity showed no significant difference (P＞0.05) at basal state,but showed significant decreases (P＜0.05) after reactive hyperemia. Single-factor correlation analysis showed that FMD was in negative correlation with disease course, TG, ISI and age (r=-0.2357,-0.2215 and -0.3256, -0.2415,(all P＜0.05～0.01),and showed no correlation of FMD with BMI, TC, FBG, HbA1c, FIns. Conclusions FMD has a value in evaluating the flow-mediated endothelial dysfunction in older T2DM patients, while our analysis of the results should consider the patient's age, gender, race, disease course, blood lipids and other factors.

Objective To assess the association of cerebrovascular reserve(CVR) with diabetes(DM)、hypertensive atherosclerotic lacunar infarction(HALI),hypertension(HT) and diabetic lacunar infarction(DLI) by means of transcranial Doppler ultrasonography (TCD) with breath-holding maneuver.Methods The breath-holding index (BHI), which was the percentage increase in middle cerebral artery(MCA) blood flow velocity as index of CVR assessment,was detected during breath-holding by TCD and breath-holding technique in 30 diabetic patients,30 hypertensive atherosclerotic lacunar infarction patients,30 hypertension patients and 30 diabetic lacunar infarction patients. Results There was significant difference in the ascending rates of Vm and BHI between diabetic group and diabetic lacunar infarction group,diabete lacunar infarction group and hypertensive atherosclerotic lacunar infarction group,hypertension group and diabetic group (all P<0.05). Conclusions Diabetes can more significantly impair CVR than hypertension. Diabetic lacunar infarction can more significantly impair CVR than diabetes. Diabetic lacunar infarction can more significantly impair CVR than hypertensive atherosclerotic lacunar infarction .

Objective To observe the association between homocysteine (Hcy)level and low limb vascular disease(LLVD) in newly-diagnosed type 2 diabetic patients. Methods The study subjects were divided into three groups : control group (NC), newly-diagnosed type 2 diabetes group without peripheral artery disease (T2DM) and peripheral artery disease with newly-diagnosed type 2 diabetes group (T2DM+LLVD).Both Hcy and the ankle-brachial index(ABI) were measured in three groups. Results Compared with NC group, clinical parameters of body mass index,waist-to-hip ratio,systolic blood pressure, total cholesterol(TC),triglycerides(TG),low density lipoprotein-cholesterol(LDL-C),and glycated hemoglobin A1C (HbA1c) increased markedly,and the content of high density lipoprotein-cholesterol (HDL-C) was markedly lower in both T2DM and T2DM+LLVD groups.In T2DM+LLVD group the contents of Hcy,LDL-C and HbA1c were markedly higher than in T2DM group,but the content of HDL-C decreased significantly.Hcy was independently associated with the development of peripheral artery disease in newly-diagnosed type 2 diabetic patients by logisitic regression analysis. Conclusions Increased Hcy is an independent risk factor for peripheral artery disease in newly-diagnosed type 2 diabetes.

Objective To compare the efficacy and safety of glargine(Lantus) versus biphasic insulin aspart 30 (30% free and 70% protamine-bound, BIAsp 30) after continuous subcutaneous insulin infusion treatment (CSII) in newly diagnosed type 2 diabetes mellitus. Methods A 20 week open and random study was performed. All 60 patients with newly diagnosed T2DM were randomly divided into two groups. Group B patients was treated by glargine and group A received treatment with BIAsp 30 administered immediately before dinner and breakfast. Blood glucose at 7 time points, glycosylated hemoglobin A1c(HbA1c) and hypoglycemia were observed. Results The postprandial glucose(PPG) was significantly lower in group B than in group A (P<0.05), and the frequency of hypoglycaemic episodes was lower in group B than in group A (P<0.05). The fasting blood glucose(FBG) was not different between two groups (P>0.05). And there was no difference between two groups in HbA1c and other adverse events. Conclusions Glargine is surperior to BIAsp30, not only in controlling the PPG but also in reducing the incidence of hypoglycemia.