Elevated Circulating LINC-P21 Serves as a Diagnostic Biomarker of Type 2 Diabetes Mellitus and Regulates Pancreatic β-cell Function by Sponging miR-766-3p to Upregulate NR3C2

2020 ◽  
Author(s):  
Zhibin Cao ◽  
Fuwang Yao ◽  
Yuqin Lang ◽  
Xueqiang Feng
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

Abstract Objective The purpose of this study was to evaluate the clinical value and biological function of long non-coding RNA (lncRNA) LINC-P21 in type 2 diabetes mellitus (T2DM), and explore the underlying mechanisms. Methods The expression of LINC-P21 was estimated using quantitative real-time PCR. The functional role of LINC-P21 was explored by gain- and loss-of-function experiments. INS-1 cell proliferation was analyzed using a cell counting kit-8 (CCK-8)assay, and the glucose-stimulated insulin secretion was measured using an ELISA kit. The miRNAs that might be sponged by LINC-P21 were analyzed, and the subsequent target genes were predicted and assessed in INS-1 cells. Results Serum expression of LINC-P21 was elevated in T2DM patients, which was correlated with fasting blood glucose levels and disease diagnosis. The glucose-stimulated insulin secretion and the proliferation of INS-1 cells were enhanced by LINC-P21 knockdown, but the overexpression of LINC-P21 led to opposite effects. miR-766-3p could be directly inhibited by LINC-P21 in INS-1 cells and reverse the effects of LINC-P21 on β-cell function. Additionally, NR3C2 was determined as a target of miR-766-3p, which could be positively regulated by LINC-P21 and had same effects with LINC-P21 on INS-1 cell proliferation and insulin secretion. Conclusion All the data demonstrated that serum elevated LINC-P21 and decreased miR-766-3p serve as candidate diagnostic biomarkers in T2DM patients. LINC-P21 acts as a potential regulator in insulin secretion and proliferation of pancreatic β-cells through targeting miR-766-3p to upregulate NR3C2.

scholarly journals Diabetic Retinopathy in Newly Diagnosed Subjects With Type 2 Diabetes Mellitus: Contribution of β-Cell Function

2016 ◽  
Vol 101 (2) ◽  
pp. 572-580 ◽  
Author(s):  
Sharmistha Roy Chowdhury ◽  
Rebecca L. Thomas ◽  
Gareth J. Dunseath ◽  
Rajesh Peter ◽  
D. Aled Rees ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Cell Function ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Β Cell Function

Impact of insulin glargine and lixisenatide on β-cell function in patients with type 2 diabetes mellitus: A randomized open-label study

2017 ◽  
Vol 19 (11) ◽  
pp. 1625-1629 ◽  
Author(s):  
Juris J. Meier ◽  
Nina Schenker ◽  
Melanie Kahle ◽  
Freimut Schliess ◽  
Christoph Kapitza ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Β Cell ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Β Cell Function

scholarly journals XOMA 052, an Anti-IL-1β Monoclonal Antibody, Improves Glucose Control and β-Cell Function in the Diet-Induced Obesity Mouse Model

2010 ◽  
Vol 31 (2) ◽  
pp. 261-261
Author(s):  
Alexander M. Owyang ◽  
Kathrin Maedler ◽  
Lisa Gross ◽  
Johnny Yin ◽  
Lin Esposito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Monoclonal Antibody ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Cell Mass ◽  
Β Cell ◽  
Diet Induced Obesity ◽  
Β Cell Function

ABSTRACT Recent evidence suggests that IL-1β-mediated glucotoxicity plays a critical role in type 2 diabetes mellitus. Although previous work has shown that inhibiting IL-1β can lead to improvements in glucose control and β-cell function, we hypothesized that more efficient targeting of IL-1β with a novel monoclonal antibody, XOMA 052, would reveal an effect on additional parameters affecting metabolic disease. In the diet-induced obesity model, XOMA 052 was administered to mice fed either normal or high-fat diet (HFD) for up to 19 wk. XOMA 052 was administered as a prophylactic treatment or as a therapy. Mice were analyzed for glucose tolerance, insulin tolerance, insulin secretion, and lipid profile. In addition, the pancreata were analyzed for β-cell apoptosis, proliferation, and β-cell mass. Mice on HFD exhibited elevated glucose and glycated hemoglobin levels, impaired glucose tolerance and insulin secretion, and elevated lipid profile, which were prevented by XOMA 052. XOMA 052 also reduced β-cell apoptosis and increased β-cell proliferation. XOMA 052 maintained the HFDinduced compensatory increase in β-cell mass, while also preventing the loss in β-cell mass seen with extended HFD feeding. Analysis of fasting insulin and glucose levels suggests that XOMA 052 prevented HFD-induced insulin resistance. These studies provide new evidence that targeting IL-1β in vivo could improve insulin sensitivity and lead to β-cell sparing. This is in addition to previously reported benefits on glycemic control. Taken together, the data presented suggest that XOMA 052 could be effective for treating many aspects of type 2 diabetes mellitus.

scholarly journals Parity and type 2 diabetes mellitus: a study of insulin resistance and β-cell function in women with multiple pregnancies

2016 ◽  
Vol 4 (1) ◽  
pp. e000237 ◽  
Author(s):  
Ditte Smed Iversen ◽  
Julie Støy ◽  
Ulla Kampmann ◽  
Thomas Schmidt Voss ◽  
Lene Ring Madsen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Multiple Pregnancies ◽  
Β Cell ◽  
Β Cell Function

Rat maternal diabetes impairs pancreatic β-cell function in the offspring

2007 ◽  
Vol 293 (1) ◽  
pp. E228-E236 ◽  
Author(s):  
Junying Han ◽  
Jianxiang Xu ◽  
Yun Shi Long ◽  
Paul N. Epstein ◽  
Ye Q. Liu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Adult Life ◽  
Maternal Diabetes ◽  
Metabolic Enzyme ◽  
Β Cell ◽  
Β Cell Function

It has been shown that maternal diabetes increases the risk for obesity, glucose intolerance, and Type 2 diabetes mellitus in the adult life of the offspring. Mechanisms for these effects on the offspring are not well understood, and little information is available to reveal the mechanisms. We studied the effect of maternal diabetes on β-cell function in the offspring of streptozotocin (STZ)-induced diabetic rat mothers (STZ-offspring). STZ-offspring did not become glucose intolerant up to 15 wk of age. At this age, however, insulin secretion was significantly impaired, as measured by in vivo and in vitro studies. Consistent with these changes, islet glucose metabolism and some important glucose metabolic enzyme activities were reduced. No significant changes were found in islet morphological analysis. These data indicate that β-cell function is impaired in adult STZ-offspring; these changes may contribute to the development of type 2 diabetes mellitus in adulthood.

scholarly journals Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control?

2008 ◽  
Vol 158 (6) ◽  
pp. 773-784 ◽  
Author(s):  
Luc F Van Gaal ◽  
Stephen W Gutkin ◽  
Michael A Nauck
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes mellitus is associated with progressive decreases in pancreatic β-cell function. Most patients thus require increasingly intensive treatment, including oral combination therapies followed by insulin. Fear of hypoglycemia is a potential barrier to treatment adherence and glycemic control, while weight gain can exacerbate hyperglycemia or insulin resistance. Administration of insulin can roughly mimic physiologic insulin secretion but does not address underlying pathophysiology. Glucagon-like peptide 1 (GLP-1) is an incretin hormone released by the gut in response to meal intake that helps to maintain glucose homeostasis through coordinated effects on islet α- and β-cells, inhibiting glucagon output, and stimulating insulin secretion in a glucose-dependent manner. Biological effects of GLP-1 include slowing gastric emptying and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more suitable pharmacokinetic properties versus GLP-1) significantly lower hemoglobin A1c, body weight, and postprandial glucose excursions in humans and significantly improve β-cell function in vivo (animal data). These novel incretin-based therapies offer the potential to reduce body weight or prevent weight gain, although the durability of these effects and their potential long-term benefits need to be studied further. This article reviews recent clinical trials comparing therapy with the incretin mimetic exenatide to insulin in patients with oral treatment failure, identifies factors consistent with the use of each treatment, and delineates areas for future research.

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