Effect of metformin on Wnt5a in individuals new-onset type 2 diabetes with different body mass indexes: The evidences from the real word research.

Aim: Metformin is a first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM), due to its inhibition of hepatic gluconeogenesis. Wingless family member 5a (Wnt5a) was significantly decreased in newly diagnosed T2DM patients and regulates secretion of ß cells through the Wnt/calcium signalling cascades. This study aims to investigate how metformin works on glucose-lowering effects in diabetes and whether the mechanism underlying it is associated with Wnt5a. Methods: A total of 144 participants were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters were evaluated in normal weight, overweight and obese new-onset T2DM subjects grouped. Results: Wnt5a was increased in overweight T2DM patients and obese T2DM patients compared with the levels in normal Body Mass Index (BMI) T2DM. The level of Wnt5a gradually increased after 3 and 6 months of metformin treatment. Among the three groups, the most significant improvement in blood glucose was observed in the obese type 2 diabetic patients, and the improvement showed a significant correlation with Wnt5a protein after patients received metformin treatment. Pearson correlation showed that there was a significant relationship between △2hOGTT and Wnt5a. After further adjusting for sex and age, a significant association existed only between Wnt5a and 2-h oral glucose tolerance test(2hOGTT), and this association was negative. Conclusion: Our results indicate that Wnt5a may play a role in the mechanism by which metformin improves blood glucose in patients with type 2 diabetes.

Effect of glucagon-like peptide-1 receptor agonist on insulin secretion index and serum Wnt5a protein in patients with new-onset type 2 diabetes mellitus.

Objective: Previous studies have found that wnt5a promotes ß-cell insulin secretion and reduced concentrations in patients with type 2 diabetes. GLP-1RA (Glucagon-like peptide-1 receptor agonists) can regulate insulin secretion. However, the evidence that GLP-1RA affect insulin secretion through the Wnt5a is inconclusive. Therefore, this study aimed to evaluate the effect of GLP-1 RA on wnt5a levels in patients with type 2 diabetes. Methods: A total of 56 onset diabetics were selected our study, 29 of them were treated by GLP-1RAs (1.2mg subcutaneous injection once a day, liraglutide, Novo Nordisk), the rest (27 case) treated by Metformin (0.5 g twice a day, Glucophage, Merck). Individuals who were using medications to manage platelet (Aspirin) and cholesterol (Statins) were enrolled and continued treatment throughout the study. Results: Our study found that the waist circumference and insulin secretion index in the GLP-1RA intervention group were significantly increased, and the insulin resistance index was lower than that of the control group. More interestingly, the serum Wnt5a protein level increased dramatically after the GLP-1RA intervention, and the level of Secreted frizzled-related protein 5 (Sfrp5) decreased compared with the control group. Multivariate linear regression analysis showed that the change of HOMA-ß (Homeostasis model assessment- ß) was significantly correlated with the changes of Wnt5a and Sfrp5, and the change of Wnt5a protein was positively correlated with HOMA-ß. Conclusion: Our results confirmed that GLP-1RA may improve HOMA-ß in patients with type 2 diabetes by affecting the level of Wnt5a protein.

Pancreatic Fat is not significantly correlated with ß-cell Dysfunction in Patients with new-onset Type 2 Diabetes Mellitus using quantitative Computed Tomography.

Objective: Type 2 diabetes mellitus (T2DM) is a chronic condition resulting from insulin resistance and insufficient ß-cell secretion, leading to improper glycaemic regulation. Previous studies have found that excessive fat deposits in organs such as the liver and muscle can cause insulin resistance through lipotoxicity that affects ß-cell function. The relationships between fat deposits in pancreatic tissue, the function of ß-cells, the method of visceral fat evaluation and T2DM have been sought by researchers. This study aims to elucidate the role of pancreatic fat deposits in the development of T2DM using quantitative computed tomography (QCT), especially their effects on islet ß-cell function. Methods: We examined 106 subjects at the onset of T2DM who had undergone abdominal QCT. Estimated pancreatic fat and liver fat were quantified using QCT and calculated. We analysed the correlations with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores and other oral glucose tolerance test-derived parameters that reflect islet function. Furthermore, correlations of estimated pancreatic fat and liver fat with the area under the curve for insulin (AUCINS) and HOMA-IR were assessed with partial correlation analysis and demonstrated by scatter plots. Results: Associations were found between estimated liver fat and HOMA-IR, AUCINS, the modified ß-cell function index (MBCI) and Homeostatic Model Assessment ß (HOMA-ß). However, no significant differences existed between estimated pancreas fat and those parameters. Similarly, after adjustment for sex, age and body mass index, only estimated liver fat was correlated with HOMA-IR and AUCINS. Conclusions: This study suggests no significant correlation between pancreatic fat deposition and ß-cell dysfunction in the early stages of T2DM using QCT as a screening tool. The deposits of fat in the pancreas and the resulting lipotoxicity may play an important role in the late stage of islet cell function dysfunction as the course of T2DM progresses.

Corrigendum to "Wingless-Type MMTV Integration Site Family Member 5a Is a Key Secreted Islet Stellate Cell-Derived Product that Regulates Islet Function".

[This corrects the article DOI: 10.1155/2019/7870109.].

Wingless-Type MMTV Integration Site Family Member 5a Is a Key Secreted Islet Stellate Cell-Derived Product that Regulates Islet Function.

BACKGROUND: Emerging evidence suggests that T2DM is attributable to the dysfunction of ß-cells and the activation of islet stellate cells (ISCs). The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled 5 (Fzd5) signalling pathway might take part in this process. Our study is aimed at defining the status of ISCs during ß-cell insulin secretion homeostasis by determining the role of the Wnt5a protein in the regulation of insulin production. We examined the effects of the status of ISCs on ß-cell insulin secretion in normoglycemic db/m and hyperglycaemic db/db mice. METHODS: iTRAQ protein screening and RNA interference were used to determine novel ISC-derived secretory products that may use other mechanisms to influence the function of islets. RESULTS: We showed a significant reduction in insulin secretion by ß-cells in vitro when they were cocultured with db/db ISCs compared to when they were cocultured with ISCs isolated from normoglycemic db/m mice; in addition, both Wnt5a and its receptor Fzd5 were more highly expressed by quiescent ISCs than by activated db/db ISCs. Treatment with exogenous Wnt5a increased the secretion of insulin in association with the deactivation of ISCs. CONCLUSION: Our observations revealed that the Wnt5a protein is a key effector of ISC-mediated improvement in islet function.