Objective To investigate the clinical characteristics and the prevalence of mitochondrial gene A3243G mutation in patients with below-40-year-old-onset type 2 diabetes mellitus in China. Methods Body mass index (BMI), waist hip ratio (WHR), metabolism control, insulin secretion and HOMA-IR were determined in 207 patients with below-40-year-old-onset diabetes mellitus and 50 subjects with normal OGTT as control. There were 117 cases with diabetic family history. The mitochondrial gene A3243G mutation was assayed by PCR-RFLP. Results TherewasnosignificantdifferenceofBMI〔(25.1?3.1) vs (24.1?3.4)kg/m 2〕 between two diabetic subgroups. The fasting blood glucose (FBG) and HbA 1c were both higher in two diabetic subgroups. Inthosepatientstheinsulin resistance was obviously (HOMA-IR 3.41～9.29). The mitochondrial gene A3243G mutation was found in one case and 5 members of her family (three cases had diabetes mellitus and two cases had normal glucose tolerance). Conclusion The prevalence of the mitochondrial gene A3243G mutatuion is 0.48% in early onset diabetic patients in China and 0.85% in positive diabetic family history patients.

Objective To observe the effect of angiotensin Ⅱ receptor blockers(ARBs)on peroxisome proliferator-activated receptor gamma(PPAR-γ)and to explore its mechanism for improving glucose and lipids metabolism.Methods Dual-luciferase gene reporting system was used to reflect PPAR-γ promoter activation by irbesartan and telmisartan.RT-PCR was used to reflect PPAR-γ mRNA by activation of irbesartan and telmisartan.Results Irbesartan and telmisartan may increase COS-7 cells PPAR-γ promoter expression and increase 3T3-L1 cells PPAR-γ mRNA expression in dose and time-dependent manners.Conclusions ARB may activate PPARs system to play a role in improving the glucose and lipids metabolism

Objective To investigate the effect of telmisartan and irbesartan on PPARα transcriptional activity, and to clarify their molecular mechanisms in improving glucose and lipid metabolism. Methods The structural expression vectors, including pCMV-PPARα, pGL3-PPRE and the internal control vector pRL-TK, were transiently eo-transfected into COS-7 cells using SuperFect, the cells were eontinously cultured with various concentrations of telmisartan and irbesartan, and then the PPRE controlled luciferase activity was determined by using a dual-luciferase reporter gene assay system. PPARα mRNA and protein expression levels were detected by RT-PCR and Western blot after 3T3-L1 adipoeytes were treated with various concentrations of telmisartan or irbesartan. Results (1) Both telmisartan and irbesartan stimulated PPARα transcriptional activity in concentration-and time-dependent manners in cultured COS-7 cells with the maximal effect at 60 h, with the results increased by 3.8 and 2.6 folds respectively at the concentration of 100 μmol/L compared with control group (both P<0.01). (2) The PPARγ antagonist GW9662 did not inhibit fenofibrate, telmisartan and irbesartan-stimulated PPARα transcriptional activities. (3) Both telmisartan and irbesartan increased PPARα mRNA and protein expression levels in a dose-dependent manner in 3T3-L1 adipocytes. Conclusion Angiotensin type 1 receptor blockers, telmisartan and irbesartan, can both increase PPARα transcriptional activity, which may contribute to their metabolic effects.

Objective To explorer the effect of angiotensin type 1 receptor blockers (ARB) on activating peroxisome proliferator-activated receptor (PPAR) ? and ?.MethodsLuciferase gene reporters of PPAR? and PPAR? were constructed in COS-7 cells.The cells were then cultured with various concentrations (0,0.01,0.1,1,10 and 100 ?mol/L) of valsartan,losartan,irbesartan or telmisartan for 12,24,36,48 and 60 hours;or co-cultured with PPAR? antagonist GW9662 (10,30?mol/L) for 1 hour,and then cultured with various concentrations (0,1 and 10?mol/L) of irbesartan or telmisartan for 12,24,36,48 and 60 hours.The peroxisome proliferator-response element (PPRE) luciferase activity was determined by Dual-Luciferase Reporter Gene Assay system.3T3-L1 cells were induced to differentiate into adipocytes,and then co-cultured with 10?mol/L of valsartan,losartan,irbesartan or telmisartan for 24 hours,and the expressions of PPAR? and PPAR? mRNA and protein were detected by RT-PCR and Western blotting respectively.ResultsStimulation of valsartan and losartan didn't increase the transcriptional activities of PPAR? and PPAR? in COS-7 cells,while of irbesartan and telmisartan significantly increased the transcriptional activity of PPAR? and PPAR? in COS-7 cells.After co-cultured with 100 ?mol/L of irbesartan or telmisartan for 48 hours,the PPAR? transcriptional activities reached their peak values (43.3?13.0 and 47.8?11.8 respectively),and were significantly higher than that of control group (4.3?0.5,P

Objective To investigate the effect of continuous subcutaneous insulin injection(CSII)and multiple subcutaneous insulin injection(MSII)on islet b cell function at the onset of type 2 diabetes.Method 64 patients were randomly divided into CSII(f/m=18/20)and MSII groups(f/m=14/12).There was no significant difference in age,fasting C peptide level,fasting blood glucose level,BMI and HbA1c.The patients of both groups were given intensive insulin therapy.Once the total dosage of daily insulin was kept less than 30U and the fast blood glucose was 3.6-6.0 mmol/L,intensive insulin therapy was changed to oral administration of hypoglycin A(OHA),otherwise the intensive insulin therapy was continued.The number of patients who were switched over to oral drug was compared after one month after the intensive therapy.Result 31 patients in CSII group and 8 patients in MSII group were changed to OHA one month after intensive therapy.A significant difference existed between the two groups(?2=3.37,P

Objective To amplify the recombinant adenovirus vector carrying rat angiotensin Ⅱ type 2 receptor (AT2R) gene using human embryonic kidney (HEK) 293A cell lines and to construct a pancreatic islet βcell model overexpressing AT2R by transfecting the adenovirus vector into rat insulinoma (INS-1) cell lines.Methods Recombinant adenovirus vector Ad-G-AT2R-EGFP and control vector Ad-CMV-EGFP were amplified with HEK 293A cells and the titer of the adenovirus was detected .After both adenovirus vectors were transfected into INS-1 cells,AT2R and angiotensin Ⅱtype 1 receptor(AT1R) gene expressions were tested using real-time PCR, Western blotting, immunofluorescence staining and confocal laser-scanning microscopy .Results The titer of amplified Ad-G-AT2R-EGFP and Ad-CMV-EGFP was re-spectively 9 ×109 pfu/ml and 8 ×109 pfu/ml.Transfection of Ad-G-AT2R-EGFP into INS-1 cells induced an increase in AT2R mRNA expression in a dose-dependent manner , and significantly increased AT2R mRNA and protein expression compared with Ad-CMV-EGFP-or mock-transfection.Conclusion The recombinant adenoviral vector carrying AT2R gene is successfully amplified and an INS-1 cell model overexpressing AT2R is constructed by transient transfection , which can contribute to further study of the role of AT2R in pancreatic islet βcells.

Objective To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVETM study.Methods Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study.Data on demographics,medical history,glycemic profile and treatment regimen at baseline were collected by physicians.Results A total of 3272 patients [female 42％,male 58％,mean age (56.2 ± 10.8) years] were included in the study.Their BMI was (25.3 ± 3.3) kg/m2.The duration of diabetes was 4.0 (0.1-27.0) years,and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0(0.0-20.2) years.The proportions of subjects with diabetic macro-and micro-vascular complications were 15.8％ (515 cases) and 27.1％ (866 cases),respectively.The hemoglobin Al c (HbAl c) at baseline was (8.33 ± 1.70) ％,and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L.Conclusions A large proportion of patients with type 2 diabetes remain in poor glycemic control,and the prevalence of diabetic complications is high,which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.