Circulating RNAs as predictive markers for the progression of type 2 diabetes

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non‐progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non‐progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes.     

Deletion of pancreatic β‐cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin‐induced hyperglycaemia

Severe reduction in the β‐cell number (collectively known as the β‐cell mass) contributes to the development of both type 1 and type 2 diabetes. Recent pharmacological studies have suggested that increased pancreatic β‐cell proliferation could be due to specific inhibition of adenosine kinase (ADK). However, genetic evidence for the function of pancreatic β‐cell ADK under physiological conditions or in a pathological context is still lacking. In this study, we crossed mice carrying LoxP‐flanked Adk gene with Ins2‐Cre mice to acquire pancreatic β ‐cell ADK deficiency (Ins2‐Cre^±Adk^fl/fl) mice. Our results revealed that Ins2‐Cre^+/‐Adk^fl/fl mice showed improved glucose metabolism and β‐cell mass in younger mice, but showed normal activity in adult mice. Moreover, Ins2‐Cre^±Adk^fl/fl mice were more resistant to streptozotocin (STZ) induced hyperglycaemia and pancreatic β‐cell damage in adult mice. In conclusion, we found that ADK negatively regulates β‐cell replication in young mice as well as under pathological conditions, such as STZ induced pancreatic β‐cell damage. Our study provided genetic evidence that specific inhibition of pancreatic β‐cell ADK has potential for anti‐diabetic therapy.     

MicroRNA‐351 eases insulin resistance and liver gluconeogenesis via the PI3K/AKT pathway by inhibiting FLOT2 in mice of gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is known as different degree glucose intolerance that is initially identified during pregnancy. MicroRNAs (miRs) may be a potential candidate for treatment of GDM. Herein, we suggested that miR‐351 could be an inhibitor in the progression of GDM via the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway. Microarray analysis was used to identify differentially expressed genes and predict miRs regulating flotillin 2 (FLOT2). Target relationship between miR‐351 and FLOT2 was verified. Gestational diabetes mellitus mice were treated with a series of mimic, inhibitor and small interfering RNA to explore the effect of miR‐351 on insulin resistance (IR), cell apoptosis in pancreatic tissues and liver gluconeogenesis through evaluating GDM‐related biochemical indexes, as well as expression of miR‐351, FLOT2, PI3K/AKT pathway‐, IR‐ and liver gluconeogenesis‐related genes. MiR‐351 and FLOT2 were reported to be involved in GDM. FLOT2 was the target gene of miR‐351. Gestational diabetes mellitus mice exhibited IR and liver gluconeogenesis, up‐regulated FLOT2, activated PI3K/AKT pathway and down‐regulated miR‐351 in liver tissues. Additionally, miR‐351 overexpression and FLOT2 silencing decreased the levels of FLOT2, phosphoenolpyruvate carboxykinase, glucose‐6‐phosphatase, fasting blood glucose, fasting insulin, total cholesterol, triglyceride, glyeosylated haemoglobin and homeostasis model of assessment for IR index (HOMA‐IR), extent of PI3K and AKT phosphorylation, yet increased the levels of HOMA for islet β‐cell function, HOMA for insulin sensitivity index and glucose transporter 2 expression, indicating reduced cell apoptosis in pancreatic tissues and alleviated IR and liver gluconeogenesis. Our results reveal that up‐regulation of miR‐351 protects against IR and liver gluconeogenesis by repressing the PI3K/AKT pathway through regulating FLOT2 in GDM mice, which identifies miR‐351 as a potential therapeutic target for the clinical management of GDM.     

Identification of Cognitive Dysfunction in Patients with T2DM Using Whole Brain Functional Connectivity

Majority of type 2 diabetes mellitus (T2DM) patients are highly susceptible to several forms of cognitive impairments, particularly dementia. However, the underlying neural mechanism of these cognitive impairments remains unclear. We aimed to investigate the correlation between whole brain resting state functional connections (RSFCs) and the cognitive status in 95 patients with T2DM. We constructed an elastic net model to estimate the Montreal Cognitive Assessment (MoCA) scores, which served as an index of the cognitive status of the patients, and to select the RSFCs for further prediction. Subsequently, we utilized a machine learning technique to evaluate the discriminative ability of the connectivity pattern associated with the selected RSFCs. The estimated and chronological MoCA scores were significantly correlated with R = 0.81 and the mean absolute error (MAE) = 1.20. Additionally, cognitive impairments of patients with T2DM can be identified using the RSFC pattern with classification accuracy of 90.54% and the area under the receiver operating characteristic (ROC) curve (AUC) of 0.9737. This connectivity pattern not only included the connections between regions within the default mode network (DMN), but also the functional connectivity between the task-positive networks and the DMN, as well as those within the task-positive networks. The results suggest that an RSFC pattern could be regarded as a potential biomarker to identify the cognitive status of patients with T2DM.     

胰岛素不同给药方式对妊娠期糖尿病患者围手术期血糖控制的效果研究

目的:研究胰岛素不同给药方式对妊娠期糖尿病患者围手术期血糖控制的效果与安全性。方法:选择2013年11月～2016年11月于我院接受治疗的92例妊娠期糖尿病患者,所有患者按随机数字表法分为对照组和研究组,每组46例。对照组围手术期予以皮下注射胰岛素治疗,研究组围手术期予以胰岛素泵治疗。比较两组空腹血糖(FBG),餐后2 h血糖(2hPBG),血糖达标情况,抗生素使用情况,切口愈合情况、住院时间及并发症的发生情况。结果:治疗后12 h、24 h及36 h,两组FBG、2hPBG水平均较治疗前显著下降,且研究组以上指标均低于对照组(P0.05)。研究组血糖达标、抗生素使用、切口愈合及住院时间均明显短于对照组(P0.05)。两组均有低血糖、切口感染发生,研究组并发症发生率低于对照组(P0.05)。结论:胰岛素泵输注胰岛素对妊娠期糖尿病患者围手术血糖的控制效果明显优于皮下注射胰岛素,且其安全性更高。     

Transcriptional Heterogeneity of Beta Cells in the Intact Pancreas

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Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes

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Insulin-Driven PI3K-AKT Signaling in the Hepatocyte Is Mediated by Redundant PI3Kα and PI3Kβ Activities and Is Promoted by RAS

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