Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients' plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3'UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.

Type 2 diabetes is characterized by a deficit in β-cell function and mass, and its incidence increases with age. Autophagy is a highly regulated intracellular process for degrading cytoplasmic components, particularly protein aggregates and damaged organelles. Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. Autophagy may be necessary to maintain structure, mass, and function of pancreatic β-cells. In this study, we investigated the effects of age on β-cell function and autophagy in pancreatic islets of 4-month-old (young), 14-month-old (adult), and 24-month-old (old) male Wistar rats. We found that islet β-cell function decreased gradually with age. Protein expression of the autophagy markers LC3/Atg8 and Atg7 exhibited a marked decline in aged islets. The expression of Lamp-2, a good indicator of autophagic degradation rate, was significantly reduced in the islets of old rats, suggesting that autophagic degradation is decreased in the islets of aged rats. However, protein expression of beclin-1/Atg6, which plays an important role in the induction and formation of the preautophagosome structure by associating with a multimeric complex of autophagy regulatory proteins (Atg14, Vps34/class 3 PI3 kinase, and Vps15), was most prominent in the islets of adult rats, and was higher in 24-month-old islets than in 4-month-old islets. The levels of p62/SQSTM1 and polyubiquitin aggregates, representing the functions of autophagy and proteasomal degradation, were increased in aging islets. 8-Hydroxydeoxyguanosine, a marker of mitochondrial and nuclear DNA oxidative damage, exhibited strong immunostaining in old islets. Analysis by electron microscopy demonstrated swelling and disintegration of cristae in the mitochondria of aged islets. These results suggest that β-cell and autophagic function in islets decline simultaneously with increasing age in Wistar rats, and that impaired autophagy in the islets of older rats may cause accumulation of misfolded and aggregated proteins and reduce the removal of abnormal mitochondria in β-cells, leading to reduced β-cell function. Dysfunctional autophagy in islets during the aging process may be an important mechanism leading to the development of type 2 diabetes.

Ursolic acid (UA) is a triterpenoid isolated from Chinese herbal medicine. It is extensively distributed in the plant kingdom in at least 63 Chinese herbal medicines of 26 families. UA has multiple bioactivities, including anti‑viral hepatitis, antitumor, anti‑oxidation, anti‑bacterium and anti‑inflammation. The aim of this in vitro study was to examine the effects of UA on diabetes‑induced nephropathy and its possible mechanism. In mice with diabetes‑induced nephropathy, UA increased the body weight, reduced kidney/body weight index, protected kidney cells, alleviated inflammation [tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 levels] and kidney cell damage. It was also indicated that UA suppressed Toll‑like receptor 4 (TLR4), myeloid differentiation factor 88 and nuclear factor‑κB protein expression in mice with diabetes‑induced nephropathy. The inhibition of TLR4 increased the anti‑inflammation of UA on inflammation in rat with diabetes‑induced nephropathy through the TLR4 signaling pathway. In conclusion, UA alleviates inflammation and inhibits diabetes‑induced nephropathy through a TLR4‑mediated inflammatory pathway. The present findings indicated that UA may be a possible therapeutic agent against diabetic nephropathy.

Aim The aim of this study was to determine the relationship between abnormal glucose metabolism and osteoporosis (OP) in Han Chinese men over the age of 50 years. Patients and methods A cross-sectional study of 775 male patients aged over 50 years was performed at our hospital in 2011. The patients were divided into a normal glucose metabolism group, an impaired glucose regulation (IGR) group, and a type 2 diabetes mellitus (T2DM) group. Differences in their bone mineral densities (BMDs), OP detection rates, and indices of bone metabolism were assessed. Results After adjusting for age and body mass index (BMI), there were no significant differences in lumbar spine, femoral neck, and total hip BMD values in the three groups ( P >0.05) nor in OP detection rates ( P =0.19). However, there were some significant differences in bone metabolism markers between the groups after adjusting for age, BMI, and serum creatinine (Cr): 25-hydroxyvitamin D (25(OH)D) was positively correlated with the presence of abnormal glycometabolism ( r =0.08; P <0.01), while β-carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX), bone gamma-carboxyglutamic acid protein (BGP; osteocalcin [OC]), and procollagen type 1 intact N-terminal propeptide (P1NP) were negatively correlated ( r =−0.13, −0.21, −0.14, respectively; P <0.01). Logistic regression analysis of the data indicated that BGP was the only bone metabolism marker significantly influenced by abnormal glucose metabolism (OR =0.96). Conclusion There were no significant differences in BMD or OP detection rates between the three glycometabolism groups after adjusting for age and BMI. However, the bone metabolism marker, BGP, was significantly negatively correlated with abnormal glucose metabolism.

Background. Previous studies have shown that the ratio of triglyceride to high-density lipoprotein cholesterol level (TG/HDL-C) is a risk factor for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the nonlinear relationship between TG/HDL-C and the incidence of T2DM in a Chinese population. Methods. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the incidence of T2DM among 7,791 participants from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) cohort study at baseline. Results. After adjusting for age, sex, body mass index, smoking status, alcohol intake, low-density lipoprotein cholesterol level, strenuous activity, education level, family histories of T2DM and tumors, and the presence of hypertension, tumor, stroke, and coronary heart disease, we showed that TG/HDL-C was positively associated with the incidence of T2DM at the 4-year follow-up ( OR = 1.49 , 95 % CI = 1.26 – 1.78 ). TG/HDL-C and incidence of T2DM showed a nonlinear relationship; the inflection point of TG/HDL-C was 1.50. The ORs (95% CI) on the left and right sides of the inflection point were 2.50 (1.70–3.67) and 0.96 (0.67–1.37), respectively. After adjusting for age, sex, and body mass index (BMI) in the linear relationship, the OR of the incidence of T2DM was 1.60 ( 95 % CI = 1.37 – 1.87 ). When the TG/HDL-C was less than 1.50 or greater than 1.76, the ORs (95% CI) were 2.41 (1.82–3.18) or 0.81 (0.53–1.25), respectively. Subgroup analysis showed no relationships of T2DM incidence with sex, BMI, family history of T2DM, or TG/HDL-C. Conclusion. TG/HDL-C is positively associated with diabetes risk. In our study, with each increasing quintile, the risk of T2DM after 4 years was 1.60 or 1.49 depending on the variables adjusted. In addition, our cohort study showed a nonlinear relationship between TG/HDL-C and T2DM incidence, with an inflection point of 1.76 or 1.50, depending on the variables adjusted. When the TG/HDL was less than 1.50, the ORs (95% CI) were 2.41 (1.82–3.18) and 2.50 (1.70–3.67). When the TG/HDL-C was greater than 1.76 or 1.50, there was no significant difference in the change in OR.