Effect of repaglinide and gliclazide on glycaemic control, early-phase insulin secretion and lipid profiles in / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Both repaglinide and gliclazide are insulin secretagogues widely used in the treatment of type 2 diabetes. They stimulate insulin secretion through distinct mechanisms and may benefit patients from different aspects. The present study was to evaluate the effects of repaglinide or gliclazide on glycaemic control, insulin secretion, and lipid profiles in type 2 diabetes patients.</p><p><b>METHODS</b>A total of 47 newly diagnosed type 2 diabetes patients were randomized 1:1 to receive a 4-week treatment with repaglinide or gliclazide. The standard mixed meal tolerance test was performed before and after the treatment. Plasma glucose (PG), insulin concentration, and lipid profiles were measured. The area under insulin concentration curve (AUC(ins)) and the early-phase insulin secretion index (ΔI(30)/ΔG(30)) were calculated.</p><p><b>RESULTS</b>After the trial, fasting and postprandial PG and postprandial insulin improved significantly in both groups (P < 0.05). The maximum insulin concentration occurred earlier in the repaglinide group than that in the gliclazide group. AUC(ins) increased in both groups (P < 0.05), but no significant difference was found between groups. ΔI(30)/ΔG(30) increased in both groups (P < 0.05), especially in the repaglinide group (P < 0.05). Triglyceride and total cholesterol decreased significantly in the repaglinide group in some time points, while no significant change was observed in the gliclazide group.</p><p><b>CONCLUSIONS</b>Repaglinide and gliclazide had similar effects on glycaemic control and total insulin secretion, while repaglinide had more effects on improvements in β-cell function and lipid metabolism.</p>

Biochemical markers of age-related changes in bones turnover and bone mineral density in healthy Chinese men / 中南大学学报(医学版)

OBJECTIVE@#To determine the relationship between bone alkaline phosphatase (BAP) and cross-linked N-telopeptides of type I collegen(NTX) and bone mineral density in healthy men aged 20-80.@*METHODS@#BAP and NTX of 389 healthy men were measured by ELISA. BMD at the lumbar spine and the hip as measured by dual energy X-ray absorptiometry. The correlation of bone biochemical markers with age and BMD fit 10 regression models.@*RESULTS@#BAP and NTX negatively correlated with age. The cubic regression model was better with age-related changes of bone biochemical markers as compared with the other regression models and the coefficients of determination of fitting curve were 0.013-0.029 (P< 0.05). The value of bone biochemical markers as the highest during 20-29 age groups, then they decreased to a nadir level in the 50-59 years age. After 60 years, bone formation markers remained stable; however resorption marker increased slightly. After adjustment for age, weight, height, BMI, and smoking, bone biochemical markers were negatively correlated with most sites of BMD.@*CONCLUSION@#BAP and NTX may be relatively sensitive and specific markers to evaluate age-related changes of bone turnover. It may benefit the prevention of osteoporosis by monitoring the level of BAP and NTX.

Effect of different glucose concentrations on the expressions of insig-1 and insig-2 mRNA during the differentiation of 3T3-L1 cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of different concentrations of glucose on the differentiation of 3T3-L(1) and the expression of insig-1 and insig-2 mRNA, and to explore the effect of insulin-induced gene in the differentiation and formation of adipocytes and lipogenesis.@*METHODS@#The 3T3-L(1) cells were induced to differentiate in high glucose concentration (25 mol/L G.S), low glucose concentration (5.5 mol/L G.S), and mannitol (19.5 mol/L Mannitol +5.5 mol/L G.S), respectively. The differentiation of 3T3-L(1) cells was examined by oil red "O" straining, and the expression of insig-1,insig-2 mRNA and AP2 mRNA was examined by RT-PCR and in situ hybridization.@*RESULTS@#With the differentiation of 3T3-L(1) cells, the expression of insig-1 and insig-2 mRNA was gradually up-regulated. The expression of insig-1 and insig-2 mRNA significantly increased while AP(2) mRNA decreased in the low glucose concentration inducing group and mannitol inducing group. In the high glucose concentration inducing group, the cell differentiation was poor (P<0.05). There was no difference between the low glucose concentration and the mannitol group in the differentiation of 3T3-L(1) cells, and in the expression of insig-1 and insig-2 and AP(2) mRNA.@*CONCLUSION@#Different concentrations of glucose may influence the cell differentiation and the low glucose concentration promotes insig-1 and insig-2 gene expression, which may lead to the inhibition of the differentiation and lipogenesis of preadipocytes.

Change in bone mineral density in female patients with hyperthyroidism / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of the course and menopause on the change of bone mineral density (BMD) in female patients with hyperthyroidism.@*METHODS@#BMDs of hip and lumbar vertebrae were measured by dual-energy X-rays absorptiometry(DEXA) in the female patients (n=192, aged 14 approximately 72). Patients were divided into 2 groups (premenopausal and postmenopausal)and 2 subgroups(short-course and long-course). The BMDs were compared between those of age-matched, weight-matched, height-matched and body mass index matched control subgroups.@*RESULTS@#In the premenopausal hyperthyroidic patients, only the BMDs of the second and total lumbar vertebrae with long-course were significantly lower than those of short-course group(P< 0.05). In the post-menopausal group with the long-course,each BMD measured had a lower level compared with that with short-course, of which the hip and the second lumber vertebrae were evident (P< 0.01).@*CONCLUSION@#The course and menopause have an effect on the BMDs in female patients with hyperthyroidism.

Effect of adiponectin on human osteoblast differentiation / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of adiponectin on the osteoblast differentiation and its signal transduction.@*METHODS@#Adipopnectin receptor (AdipoR) was detected by immunoblot analysis. Alkaline phosphatase (ALP) activity was measured by enzyme-linked immunosorbent assay. Osteocalcin was measured by a specific radioimmunoassay kit, and the extent of mineralized matrix was determined. RNA interference was used to down-regulate the expression of AdipoR1 in human osteoblasts, and the effect of adiponectin on osteoblast differentiation was investigated.@*RESULTS@#Only AdipoR1 protein was detected in human osteoblasts. Adiponectin could promote osteoblast differentiation, and result in a dose-dependent increase in ALP activity, osteocalcin secretion, and an increase in mineralized nodules. Suppression of AdipoR1 with siRNA could abolish the adiponectin induced ALP expression. Adiponectin could induce the activation of p38 and JNK, but not ERK1/2 in osteoblasts, and the pretreatment of osteoblasts with the p38 inhibitor (SB203580) could block the adiponectin-induced ALP activity.@*CONCLUSION@#Adiponectin can induce human osteoblast differentiation via AdipoR1/p38 pathway.

Serum leptin with bone mineral density and body fat mass in males / 中南大学学报(医学版)

OBJECTIVE@#To determine the relationship of serum leptin concentration and bone mineral density(BMD), body fat mass in males.@*METHODS@#Plasma concentrations of leptin in 350 Chinese males, aged 20 to 80 years were measured with ELISA; BMD values at lumbar spine, hip and total body BMD, and body composition, including lean tissue mass (LTM) and fat tissue mass (FTM), were measured using dual-energy-X-ray absorptiometry (DXA). The relationship between changes in serum leptin concentration with age, body weight, body mass index, body fat mass, and BMD values at 5 skeletal sites was fit by 10 regression models, and the models giving the best fit were selected.@*RESULTS@#The S regression model best described the changes in serum leptin level with age (R(2)=0.104, P<0.009), while the compound regression model best described the changes in serum leptin concentration with BMI and weight (R(2)=0.296, P<0.001; R(2) =0.304, P<0.001). Leptin concentration was correlated with FTM (R(2)=0.448, P<0.001) and rate of body fat(R(2)=0.461, P<0.001). The serum leptin level was significantly correlated with BMD of multiple skeletal sites (R(2) was 0.115 for anterior spine BMD, 0.102 for lateral spine BMD,0.098 for femoral neck BMD, 0.112 for total hip BMD, respectively). In a multivariate analysis, leptin concentration was not a significant predictor of BMD at any site.@*CONCLUSION@#Serum leptin concentration correlates with body fat mass and percentage of body fat, but is not a significant predictor of BMD at any site in Chinese males.

Apoptosis of mesenchymal cell line MBA-1 induced by core binding factor alpha 1 / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of two core binding factors alpha 1 (Cbfa1) isfroms (Cbfa1/P56 and Cbfa1/P57) on the apoptosis of mesenchymal cell line MBA-1.@*METHODS@#The two Cbfal isfroms were transiently transfected into MBA-1 cells, then the changes of apoptosis rate were observed by flow cytometer. The protein expressions of Cbfa1, Bax, Bcl-2, caspase-3, and caspase-9, cytochrome-C and TNF-alpha were determined by Western immunoblot.@*RESULTS@#After the transient transfection with the two isforms of Cbfa1, MBA-1, the cells apoptotic rates increased, and the ratio of Bax/Bcl-2, the expressions of cytochrome-C, caspase-3, caspase-9, and TNF-alpha were significantly increased.@*CONCLUSION@#Cbfa1 can promote the apoptosis in mesenchymal cell line MBA-1. Bax/Bcl-2, cytochrome-C, caspase-9, caspase-3, and TNF-alpha are also involved in the apoptosis pathway.

Effect of PTH gene polymorphism on bone mineral density in normal females / 中华内分泌代谢杂志

Objective To evaluate the effect of PTH gene polymorphisms on bone mineral density (BMD) at multiple skeletal sites in normal females.Methods PTH gene phenotype was determined by PCR-RFLP of restriction enzyme Bst BⅠin 596 females aged (46.3?13.7) years (20-80 years),and PCR products with or without enzymolytic site were considered as genotype B or genotype b respectively.BMDs of the anteropesterior spine (AP) and supine lateral spine (Lat) of lumbar vertebrae (L_1-L_4),femoral neck (FN),total hip (T-hip), Ward's triangle (Ward),Trochanter (Troch),forearm [radius+ulna ultradistal (RUUD) and total area of radius + ulna (RUT) ] were measured by DEXA (QDR4500A).Results (1) Hardy-Weinberg equilibrium was evident for PTH polymorphisms.The frequencies of genotype were BB 0.784,Bb 0.208,bb 0.008 and frequencies of alleles B,b were 0.888 and 0.112 respectively in 596 normal females.Frequencies of BB,Bb,bb genotypes were 0.781,0.210,and 0.009 respectively in 347 postmenopausal women and their frequencies of alleles B,b were 0.886,0.114.No significant difference was found between post- and premenopausal women in genotype frequen- cy.(2) Comparing their BMDs of AP,Lat,FN,T-hip,Ward,Troch,RUUD and RUT,there was no significant difference between BB and Bb genotypes of pre- and postmenopansal women groups.(3) Logistic regression analysis failed to show any statistical difference between normal and osteoporosis women with regard to PTH phenotype.Conclusion PTH gene polymorphism has little effect on BMD in normal females.

Effects of genistein and 17?-estradiol on microstructure of cancellous bone in ovariectomized rats / 中华内分泌代谢杂志

Objective To observe the effects of genistein and 17?-estradiol on microstructure of cancellous bone in ovariectomized (OVX) rats.Methods Ninty 7-month-old SD rats were randomly divided into baseline group,ovariectomized (OVX),sham-operated (SHAM),17?-estradiol treated (10?g?kg~(-1).day~(-1),EST) and genistein treated (5 mg?kg~(-1)?day~(-1),GEN) groups,and were killed at the beginning of the experiment,the 3rd and 15th week after operation.MicroCT scanning was performed on the left tibia in vitro.The regions involving 0.5 mm slice thickness and 1.6 mm distal to the tibial growth plate were selected as the regions of interest.Results At the 3rd week after operation,the tissue bone mineral density (tBMD) and trabecular thickness (sTh.Th) in group GEN were significantly higher than those in OVX and EST groups (all P

Effect of apelin on human osteoblasts / 中华内分泌代谢杂志

Objective To observe apelin and its receptor (APJ) expressions in human osteoblasts and evaluate the effect of apelin on osteoblasts.Methods The expressions of apelin and APJ in human osteoblasts were tested by RT-PCR and Western blot.After human osteoblasts were treated with apelin,cell proliferation was measured by [~3H] thymidine incorporation and cell counting.Cell function was measured by alkaline phosphatase (ALP) activity,the secreted osteocalcin level and typeⅠcollagen production .The activation of signaling cascades was tested by Western blot.Small-interfering RNA (siRNA) to blockade APJ was applied to observe effects of apelin on cell proliferation and the activation of signaling cascades.Results Both apelin and APJ were expressed in human osteoblasts.Apelin increased the proliferation and did not show the influences on ALP activity, osteocalcin secretion and type I collagen production in human osteoblasts.Apelin induced activation of phosphatidylinositol-3 kinase (PI3K) downstream effector (Akt),but not mitogen-activated protein kinase (MAPK) such as c-jun N-terminal kinase (JNK),p38 and ERK1/2 in human osteoblasts.Suppression of APJ with siRNA or LY294002 (PI3K inhibitor) abolished the apelin-induced cell proliferation and the activation of Akt.Conclusion Human osteoblasts express apelin and APJ.Apelin stimulates the proliferation of human osteoblast via APJ/PI3K/Akt pathway,but has no effect on osteoblast differentiation.