ABSTRACT
Objective To study the effect and mechanism of forkhead transcriptionfactor O1( FoxO1) on proliferation of rat mesangial cells(MCs) cultured under high glucose conditions. Methods Constructing lentiviral vectors of LV-CA-FoxO1 and LV-siRNA-FoxO1 were used to upregulate or downregulate FoxO1. Moreover, negative control LV-NC-FoxO1 was also constructed. Rat MCs were separately cultured in normal glucose(5. 6 mmol/ L, NG group), only high glucose(30 mmol/ L, HG0 group), LV-NC-FoxO1 with HG(HG1 group),LV-CA-FoxO1 with HG (HG2 group), and LV-siRNA-FoxO1 with HG(HG3 group) for 72 h. MTT assay and flow cytometrywas were used to analyze cell proliferation and cell cycle distribution. The expression of FoxO1, cyclin-dependent kinase inhibitor (p27), cyclinD1, and cyclin-dependent kinase 4( CDK4) were detected by QRT-PCR and Western blot. Results The MCs proliferation rate in HG0 group was faster than that in NG group. Besides, there were no statistical differences in FoxO1 expression and proliferation rate of MCs between HG0 group and HG1 group. Nevertheless, LV-CA-FoxO1 promoted cell cycle arrest at the G1 phase and attenuated proliferation rate, along with upregulation of FoxO1 and p27 and downregulation of cyclin D1 and CDK4 in HG2 group ( all P < 0. 05). Moreover, degradation of FoxO1 by LV-siRNA-FoxO1 stimulated hyperproliferation of MCs, associating with decline of p27 and increase of cyclin D1 and CDK4 in HG3 group(all P<0. 05). Conclusion The proliferation of MCs induced by high glucose is regulated by utilizing transgenic technology targeted and regulated FoxO1 expression and consequently through FoxO1 / p27 signaling pathway. These findings indicate that FoxO1 seems to be a new therapeutic target for early diabetic nephropathy.
ABSTRACT
Objective To investigate the prevalence and features of thyroid nodules in middle and aged patients with type 2 diabetes mellitus(T2DM). Methods High-resolution ultrasonography was used to detect thyroid nodules in 132 cases middle and aged patients with type 2 diabetes and 89 patients without diabetes.The nodule features and its relationships with related indicators in diabetic patients were analyzed. Results The prevalence of thyroid nodules in middle and aged patients with type 2 diabetes was higher than that without diabetes (67.4％ vs. 53.9％,P＜0.05),and most occurred in 50 to 59 age group (66.7％ vs. 42.9％) without dependence on changes in thyroid functions and volumes.In diabetes group,the prevalence of thyroid nodules were 59.5％ in male and 81.3％ in female (P＜0.05),no obvious difference was observed in the size and number of thyroid nodules between male and female,multiple nodules and micronodule (＜ 1.0 cm) had the higher incidences in both sexes.The prevalence of thyroid nodules was increased with aging,but not with diabetes duration and glycosylated hemoglobin (HbAlc) level (x2 =0.797,P=0.372; x2 =1.078,P =0.229). Conclusions It is common that thyroid nodules combined with diabetes in middle and aged patients,thyroid ultrasound screening and regular following-up of patients aged ≥50 years have important clinical significance.
ABSTRACT
Objective To investigate the characteristics of the blood glucose fluctuation in elderly patients with type 2 diabetes mellitus (T2DM). Methods The 92 elderly patients with T2DM (the elderly group) and 58 young and middle-aged patients with T2DM (the non-elderly group) were monitored using the continuous glucose monitoring system(CGMS). The characteristics of glucose profiles of the two different age groups, and of the different glycosylated hemoglobin (HbA1c) level groups in the elderly were comparatively analyzed. Results (1)There was no significant difference in HbA1c level between the elderly group and the non-elderly group. Compared with the non-elderly group, the elderly group showed the increases in blood glucose fluctuant coefficient [BGFC, (2.68±1.00) mmol/L vs. (2.12±0.74) mmol/L, t=-3.691, P＜0.001], in postprandial glucose excursion (PPGE) of breakfast and supper [(5.96±2.47) mmol/L vs. (5.11±2.44) mmol/L, t=-2.058, P＜0.05; (5.17±2.15) mmol/L vs. (4.16±2.28) mmol/L, t=-2.730, P＜0.01], in the time to postprandial glucose peak of breakfast and lunch [(112.5±29.7) min vs. (97.0±27.2) min, t=-3.225, P＜0.01; (140.0±39.7) min vs. (118.1±42.6) min, t=-3.195, P＜0.01], in the frequency of hypoglycemia (26.3% vs. 5.5%, P＜0.05), and showed the largest amplitude of glycemic excursions [LAGE, (9.66±2.48) mmol/L vs.(8.40±3.13) mmol/L, t=-2.720, P＜0.01]. (2)In the elderly, along with decreased HbA1c, the incidence of hypoglycaemia increased (P＜0.05); And along with increased HbA1c, the amplitude of blood glucose fluctuation increased. There were significant differences in BGFC, PPGE of breakfast and lunch, and LAGE among different HbA1c level groups (P＜0.01, P＜0.05, P＜0.05, P＜0.001). (3)HbA1c was positively correlated with FBG, mean blood glucose (MBG), percentage of time at glycemia (PT7.8, PT11.1), the lowest blood glucose (LBG), the highest blood glucose (HBG), BGFC, PPGE and LAGE (r=0.899-0.289, all P＜0.001). Multiple stepwise regression analysis indicated that MBG, FBG and PT7.8 was the independent influential factor of HbA1c (adjusted R2=0.807, P＜0.05). Conclusions The elderly patients with T2DM are at a particularly high risk for postprandial hyperglycemia and nocturnal hypoglycemic episodes, CGMS could show glucose fluctuation characters of T2DM patients diurnally, and provide a clinical basis for reasonable therapy.
ABSTRACT
Objective To study the effect of inflammatory cytokines on diabetic nephropathy.Methods Blood glucose(BG),blood urea nitrogen(BUN),serum creatinine(Scr) and 24 hour urinary protein(24hUPro) were detected at the end of 4 weeks and 8 weeks study in male SD rats.The rats were divided into diabetes(DM) group and normal control(NC) group.Kidney weight/body weight ratio(KI) of rats were measured and calculated.Kidney pathological changes were observed by light microscope and electron microscope.Expressions of interleukin-18(IL-18),intercellular adhesion molecule-1(ICAM-1)and tumor necrosis factor-alpha(TNF-?) in glomeruli were detected by immunohistochemical staining.Results Compared with homochronous NC group,BG,KI,24hUPro,Scr and expressions of IL-18,ICAM-1,TNF-? were significantly higher in DM group(P
ABSTRACT
Objective To investigate protective effects of pyrrolidine dithiocarbamate (PDTC) and mycophenolate mofetil (MMF) on kidneys of diabetic rats and the possible mechanism. Methods Thirty-four streptozotocin-induced diabetic rats were randomly divided into 4 groups: diabetic aminals without treatment (D group), diabetic rats treated with PDTC (P group), diabetic rats treated with MMF (M group), diabetic rats treated with combined PDTC and MMF (P+M group), and normal rats were considered as control group (C group). Blood glucose, blood urea nitrogen (BUN), serum creatinine (Scr), and 24 h urinary protein (24 h UP) were detected at the end of treatment lasting for 8 weeks. Kidneys were weighed in order to measure kidney weight/body weight ratio (KI) after rats were killed. Pathological changes in the kidneys were observed by light microscope and electron microscope. Expressions of interleukin-18 (IL-18), intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in renal glomerulus were detected by immunohistochemical staining.Results Blood glucose, BUN, Scr, 24 h UP, KI were significantly higher in D, P, M and P+M groups than those in C group (all P＜0.05). BUN, Scr, 24 h UP, KI were significantly lower in P, M and P+M groups than those in D group (all P＜0.05). 24 h UP was reduced in P+M groups compared with P,M groups (P＜0.05). Pathological changes were attenuated in P,M and P+M groups compared with D group. Expressions of IL-18, ICAM-1, TNF-α in renal glomerulus were much higher in D group than those in C group (all P＜0.05) and were reduced in P, M and P+M groups compared with D group (all P＜0.05). Expressions of IL-18, ICAM-1, TNF-α in P+M group were lower than those in P group (all P＜0.05), while expressions of IL-18, TNF-α were lower than those in M group (both P＜0.05). Conclusion The protective effects on kidneys of diabetic rats produced by combined use of PDTC with MMF were much better than by the application of either PDTC or MMF alone. The mechanism appears to be related with suppressing expressions of inflammatory cytokines.