Micro-RNA 206 affects glucose induced insulin secretion under high-fat diet

2015 ◽  
Vol 241 (1) ◽  
pp. e83
Author(s):  
M. Vinod ◽  
J.V. Patankar ◽  
V. Sachdev ◽  
W.A.E.L. Al-Zoughbi ◽  
G. Höfler ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
High Fat Diet ◽  
Micro Rna ◽  
High Fat

scholarly journals Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Camila Lubaczeuski ◽  
Luciana Mateus Gonçalves ◽  
Jean Franciesco Vettorazzi ◽  
Mirian Ayumi Kurauti ◽  
Junia Carolina Santos-Silva ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Insulin Clearance ◽  
Protein Diet ◽  
Low Protein Diet ◽  
High Fat ◽  
Insulin Degrading Enzyme ◽  
Low Protein

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

scholarly journals IP6-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hong Lin ◽  
Yuan Yan ◽  
Yifan Luo ◽  
Wing Yan So ◽  
Xiayun Wei ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
High Fat Diet ◽  
E3 Ligase ◽  
Human Islets ◽  
Cop9 Signalosome ◽  
Congenital Hyperinsulinism ◽  
High Fat ◽  
Transcriptional Suppressor

AbstractCOP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1–CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2WT/K70E mice with partially disrupted binding of IP6, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4COP1 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4COP1 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2WT/K70E, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4COP1-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP6-assisted CSN-COP1 competition. Deregulation of the IP6-CSN-CRL4COP1-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.

scholarly journals Semi-modified okara whey diet increased insulin secretion in diabetic rats fed a basal or high fat diet

2020 ◽  
Author(s):  
Ahmed E. Abdel-Mobdy ◽  
Marwa S. Khattab ◽  
Ebtesam A. Mahmoud ◽  
Eman R. Mohamed ◽  
Emam A. Abdel-Rahim
Keyword(s):  
Insulin Secretion ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
High Fat

Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMs) in diabetic mice after prolonged high-fat diet

2016 ◽  
Vol 146 (1) ◽  
pp. 13-31 ◽  
Author(s):  
Viviane Tannuri F. L. Falcão ◽  
Daniela A. Maschio ◽  
Camila Calvo de Fontes ◽  
Ricardo B. Oliveira ◽  
Junia C. Santos-Silva ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Insulin Secretion ◽  
Adhesion Molecules ◽  
Pancreatic Islet ◽  
High Fat Diet ◽  
Cell Adhesion Molecules ◽  
Diabetic Mice ◽  
High Fat

scholarly journals SUN-658 CHL1 Increases Insulin Secretion&Negatively Regulates the Poliferation of Pancreatic β Cell

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tao Yang ◽  
Qi Fu ◽  
Hemin Jiang
Keyword(s):  
Cell Cycle ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Nod Mice ◽  
Pancreatic Β Cell ◽  
High Fat ◽  
Β Cells ◽  
Β Cell ◽  
Min6 Cells

Abstract CHL1 Increases Insulin Secretion & Negatively Regulates The Poliferation Of Pancreatic β Cell Objective: CHL1 belongs to neural recognition molecules of the immunoglobulin superfamily, is mainly expressed in the nervous system. CHL1 is involved in neuronal migration, axonal growth, and dendritic projection. RNA sequencing of single human islet cells confirmed that CHL1 had an expression difference in β cells of type 2 diabetes and healthy controls. However, whether CHL1 gene regulates islet function remained to be explored. Methods: PCR and Western Blot were applied to investigate the tissue distribution of CHL1 in wild-type C57BL/6J mice. The islet expression of CHL1 gene was observed in pancreatic islets of NOD mice and high-fat-diet C57BL/6J mice of different ages. MIN6 cells with siRNA to silence CHL1 or with lentivirus to overexpress CHL1 were constructed. Effects of the gene on proliferation, apoptosis, cell cycle and insulin secretion were determined by using CCK8, EdU, TUNEL, AV/PI, GSIS, electron microscopy and flow cytometry. Results: CHL1 was localized on the cell membrane and expressed in the nervous system, islet of pancreas and gastrointestinal tract. CHL1 was hypoexpressed in the pancreatic islets of obese mice, hyperexpressed in the pancreatic islets of NOD mice and in vitro after treated with cytokines. After silencing CHL1 in MIN6 cells, insulin secretion decreased in 20 mM glucose with down-regulation of INS1, SLC2A2 gene, and transmission electron microscope showed the number of insulin secretary granules <50nm from the cell membrane was significantly reduced. Silencing of CHL1 in MIN6 cells induced cell proliferation, reduced apoptosis rate, prolonged the S phase of cell cycle and shortened the G1 phase with downregulated expression of p21, p53 and up-regulated expression of cyclin D1, opposite results were found in CHL1 over-expressing MIN6 cells. Proliferation induced by silencing of CHL1 was inhibited by ERK inhibitor (PD98059), which indicates that ERK pathway is essential for signaling by these molecules in pancreatic β cell. Conclusion: The expression of CHL1 gene was significantly decreased in the pancreatic islets of obese mice induced by high-fat diet. The low expression of CHL1 gene promotes the proliferation of MIN6 cells through the ERK pathway and affect cell cycle through the p53 pathway. This may be one of the mechanisms that pancreatic β cells compensatory hyperplasia in the stage of obesity-induced pre-diabetes.

scholarly journals The long non-coding RNA Pax6os1/PAX6-AS1 modulates pancreatic β-cell identity and function

2020 ◽  
Author(s):  
Livia Lopez-Noriega ◽  
Rebecca Callingham ◽  
Aida Martinez-Sánchez ◽  
Grazia Pizza ◽  
Nejc Haberman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
High Glucose ◽  
High Fat Diet ◽  
High Fat ◽  
Β Cell ◽  
And Function

AbstractLong non-coding RNAs (lncRNAs) are emerging as crucial regulators of β-cell development and function. Consequently, the mis-expression of members of this group may contribute to the risk of type 2 diabetes (T2D). Here, we investigate roles for an antisense lncRNA expressed from the Pax6 locus (annotated as Pax6os1 in mice and PAX6-AS1 in humans) in β-cell function. The transcription factor Pax6 is required for the development of pancreatic islets and maintenance of a fully differentiated β-cell phenotype. Pax6os1/PAX6-AS1 expression was increased in pancreatic islets and β-cell lines at high glucose concentrations, in islets from mice fed a high fat diet, and in those from patients with type 2 diabetes. Silencing or deletion of Pax6os1/PAX6-AS1 in MIN6 cells and EndoC-βH1cells, respectively, upregulated β-cell signature genes, including insulin. Moreover, shRNA-mediated silencing of PAX6-AS1 in human islets not only increased insulin mRNA, but also enhanced glucose-stimulated insulin secretion and calcium dynamics. In contrast, inactivation of Pax6os1 in mice was largely without effect on glucose homeostasis, though female Pax6os1 null mice on high fat diet (HFD) showed a tendency towards enhanced glucose clearance. Together, our results suggest that increased expression of PAX6-AS1 at high glucose levels may contribute to β-cell dedifferentiation and failure in some forms of type 2 diabetes. Thus, targeting PAX6-AS1 may provide a promising strategy to enhance insulin secretion and improve glucose homeostasis in type 2 diabetes.

scholarly journals AAV8-mediated gene transfer of microRNA-132 improves beta cell function in mice fed a high-fat diet

2019 ◽  
Vol 240 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Niels L Mulder ◽  
Rick Havinga ◽  
Joost Kluiver ◽  
Albert K Groen ◽  
Janine K Kruit
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Gene Transfer ◽  
Beta Cell ◽  
Beta Cells ◽  
High Fat Diet ◽  
Beta Cell Function ◽  
Cell Function ◽  
Beta Cell Proliferation ◽  
High Fat

MicroRNAs have emerged as essential regulators of beta cell function and beta cell proliferation. One of these microRNAs, miR-132, is highly induced in several obesity models and increased expression of miR-132 in vitro modulates glucose-stimulated insulin secretion. The aim of this study was to investigate the therapeutic benefits of miR-132 overexpression on beta cell function in vivo. To overexpress miR-132 specifically in beta cells, we employed adeno-associated virus (AAV8)-mediated gene transfer using the rat insulin promoter in a double-stranded, self-complementary AAV vector to overexpress miR-132. Treatment of mice with dsAAV8-RIP-mir132 increased miR-132 expression in beta cells without impacting expression of miR-212 or miR-375. Surprisingly, overexpression of miR-132 did not impact glucose homeostasis in chow-fed animals. Overexpression of miR-132 did improve insulin secretion and hence glucose homeostasis in high-fat diet-fed mice. Furthermore, miR-132 overexpression increased beta cell proliferation in mice fed a high-fat diet. In conclusion, our data show that AAV8-mediated gene transfer of miR-132 to beta cells improves beta cell function in mice in response to a high-fat diet. This suggests that increased miR-132 expression is beneficial for beta cell function during hyperglycemia and obesity.

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