Objective. To investigate the effect of dapagliflozin (DAPA) on cardiac hypertrophy induced by type 2 diabetes mellitus (T2DM) and its mechanism. Methods. SD rats with T2DM were divided into a T2DM group ( n = 6 ) and DAPA group ( n = 6 ). They were, respectively, fed with the same amount of normal saline and 1 mg/kg DAPA. The control group ( n = 6 ) was also fed with normal saline. The hearts were tested by the application of echocardiography and hemodynamics. Subsequently, fasting blood glucose (FBG), serum total cholesterol (TC), and triglyceride (TG) as well as interleukin- (IL-) 10, IL-6, and tumor necrosis factor (TNF)-α in serum were tested. H&E and Masson staining was performed to observe the degree of cardiac tissue lesions, and expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), calpain-1, p-IκBα, and p65 in myocardial tissue was tested by qRT-PCR and Western blot. Results. Compared with the control group, rats in the T2DM group exhibited significant diabetic symptoms: FBG was significantly elevated, and the levels of TC, TG, IL-6, and TNF-α were significantly increased, while the levels of IL-10 and the calpain activity were evidently decreased. However, DAPA treatment could improve the above changes. At the same time, the damage and fibrosis of the heart tissue in the DAPA group were markedly improved. Additionally, the mRNA expression of ANP and BNP in myocardial tissue of the DAPA group was markedly increased. And DAPA could inhibit the expression of p-IκBα/IκBα in the cytoplasm and p65 in the nucleus as well as the expression of calpain-1 in myocardial tissue. Conclusion. DAPA treatment ameliorates the cardiac hypertrophy caused by T2DM by decreasing body blood glucose, while reducing the expression of calpain-1 in cardiomyocytes and inhibiting the nuclear translocation of NF-κB.

The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present study, we explored a novel protocol that reprogrammed primary hepatocytes into functional IPCs by using multicistronic vectors carrying pancreatic and duodenal homeobox-1 (Pdx1), neurogenin 3 (Ngn3), and v-musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). These triple-transfected cells activated multiple beta-cell genes, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated manner in vitro. Furthermore, when transplanted into streptozotocin-induced diabetic mice, the cells markedly ameliorated glucose tolerance. Our results indicated that ectopic expression of Pdx1, Ngn3, and MafA facilitated hepatocytes-to-IPCs reprogramming. This approach may offer opportunities for treatment of DM.

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The roles of gene polymorphisms in diabetes mellitus (DM) have been intensively analyzed earlier, but the results of these studies were conflicting. Hence, we performed this study to better assess the relationship between genetic variations and DM. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess correlations between polymorphisms and DM. A total of 32 studies were finally included in our analyses. Significant associations with the risk of DM were detected for the rs1800871, rs1800872, and rs1800896 polymorphisms. As for complications in DM, significant association with the risk of diabetic nephropathy (DN) was detected for the rs1800871 polymorphism. In addition, we also found that the rs1800896 polymorphism was significantly associated with the risk of diabetic retinopathy (DR). Further stratified analyses on the basis of type of disease demonstrated that the positive results were predominantly driven by the T2DM subgroup. When we stratified data based on ethnicity of participants, we found that the rs1800871 polymorphism was significantly correlated with DM in Caucasians, the rs1800872 polymorphism was significantly correlated with DM in Asians, and the rs1800896 polymorphism was significantly correlated with DM in both Caucasians and Asians. Our findings indicate that rs1800871, rs1800872, and rs1800896 polymorphisms may serve as genetic biomarkers of DM. Moreover, the rs1800871 and rs1800896 polymorphisms may also contribute to the development of complications in DM.

Aims: This study investigated the association of capillary blood glucose (CBG)-assessed time in range (TIR) (3.9-10.0 mmol/L) with insulin sensitivity and islet b-cell function. Materials and Methods: We recruited 455 patients with type 2 diabetes mellitus. Seven-point glucose-profile data (pre-and 120 min post-main meals, bedtime) were collected over three consecutive days. Plasma glucose and serum insulin concentrations were measured at 0, 60, and 120 min after a 100 g standard steamed bread meal test. The homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index were computed to evaluate insulin resistance. The HOMA of b-cell function (HOMA-b) and the area under the curve between insulin and blood glucose (IAUC 0-120 /GAUC 0-120 ) were used to estimate b-cell function. Results: TIR was positively correlated with the 60 and 120 min insulin values, IAUC 0-120 , the Matsuda index, HOMA-b, and IAUC 0-120 /GAUC 0-120 (r s : 0.154, 0.129, 0.137, 0.194, 0.341, and 0.334, respectively; P < 0.05) but inversely correlated with HOMA-IR (r s : -0.239, P < 0.001). After adjusting for confounders, multinomial multiple logistic regression analysis revealed that the odds ratios (ORs) of achieving the target time in range (>70%) increased by 12% (95% confidence interval [CI]: 3-21%), 7% (95% CI: 1-14%), 10% (95% CI: 5-16%), and 45% (95% CI: 25-68%) for each 10 mIU/L increase in the 60 and 120 min insulin values, 10 unit increase in HOMA-b, and unit increase in IAUC 0-120 /GAUC 0-120 , respectively (P < 0.05). Nevertheless, the OR decreased by 10% (95% CI: 1-18%) for each unit increase in HOMA-IR (P < 0.05). Conclusions: Insulin resistance and islet b-cell function are related to capillary blood glucose-assessed TIR.Jingwen Ye and Jiajin Deng contributed equally to this work.

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ObjectiveThe purpose of this meta analysis was to assess the correlation between CDKAL1 rs10946398C>A single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) susceptibility by pooling the open published studies.MethodElectronic searching of PubMed, EMBASE, Medline, Cochrane, China Biology Medicine disc (CBM) and China National Knowledge Infrastructure (CNKI) databases were performed by two reviewers independently to collect the open published studies related to CDKAL1 rs10946398C>A single nucleotide polymorphism and T2DM susceptibility. The association between CDKAL1 rs10946398C>A single nucleotide polymorphism and T2DM susceptibility was expressed by odds ratio (OR) and the corresponding 95% confidence interval (95%CI).ResultsThirteen studies with a total of 13,966 T2DM and 14,274 controls were finally included for analysis in this meta-analysis. Of the included 13 publications, 2 studies were carried out in Europe, 8 in Asia, 2 in Africa and 1 in Latin America. Being significant statistical heterogeneity, the data was pooled through random effect model. In a dominant genetic model, there was significant correlation between CDKAL1 rs10946398C>A SNP and T2DM risk (OR=1.22, P<0.05). In a dominant genetic model people with CC or CA genotype had increased risk of developing T2DM; Because of statistical heterogeneity for the included studies in a recessive genetic model (AA+CA vs CC), the data was calculated by random effect method. The combined data showed people with AA or CA genotype had decreased risk of developing T2DM compared to CC genotype (OR=0.83, P<0.05); For a homozygous genetic model (CC vs AA), the OR was calculated through random effect model for statistical heterogeneity among the included 13 studies. The combined OR was 1.33 which indicated people with CC genotype had increased risk of developing T2DM.ConclusionAccording to the present results, CDKAL1 rs10946398C>A single nucleotide polymorphism had correlation with the susceptibility of type 2 diabetes mellitus.

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