scholarly journals Obesity-Induced miR-455 Upregulation Promotes Adaptive Pancreatic β-cell Proliferation Through the CPEB1/CDKN1B Pathway

Diabetes ◽  
2022 ◽  
Author(s):  
Qianxing Hu ◽  
Jinming Mu ◽  
Yuhong Liu ◽  
Yue Yang ◽  
Yue Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Expansion ◽  
Binding Protein ◽  
Pancreatic Β Cell ◽  
Loss Of Function ◽  
Metabolic Demand ◽  
Β Cell ◽  
Element Binding Protein ◽  
Mirna Pathway

Pancreatic β-cell adapt to compensate for increased metabolic demand during obesity. Although the microRNA (miRNA) pathway has an essential role in β-cell expansion, whether it is involved in adaptive proliferation is largely unknown. First, we report that EGR2 binding to the miR-455 promoter induced miR-455 upregulation in the pancreatic islets of obesity mouse models. Then, in vitro gain- or loss-of-function studies showed that miR-455 overexpression facilitated β-cell proliferation. Knockdown of miR-455 in ob/ob mice via pancreatic intraductal infusion prevented compensatory β-cell expansion. Mechanistically, our results revealed that increased miR-455 expression inhibits the expression of its target cytoplasmic polyadenylation element binding protein 1 (CPEB1), an mRNA binding protein that plays an important role in regulating insulin resistance and cell proliferation. Decreased CPEB1 expression inhibits elongation of the poly-A tail and the subsequent translation of Cdkn1b mRNA, reducing the CDKN1B expression level and finally promoting β-cell proliferation. Taken together, our results show that the miR-455/CPEB1/CDKN1B pathway contributes to adaptive proliferation of β-cells to meet metabolic demand during obesity.

scholarly journals Obesity-Induced miR-455 Upregulation Promotes Adaptive Pancreatic β-cell Proliferation Through the CPEB1/CDKN1B Pathway

2022 ◽  
Author(s):  
Ada Admin ◽  
Qianxing Hu ◽  
Jinming Mu ◽  
Yuhong Liu ◽  
Yue Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Expansion ◽  
Binding Protein ◽  
Pancreatic Β Cell ◽  
Loss Of Function ◽  
Metabolic Demand ◽  
Β Cell ◽  
Element Binding Protein ◽  
Mirna Pathway

Pancreatic β-cell adapt to compensate for increased metabolic demand during obesity. Although the microRNA (miRNA) pathway has an essential role in β-cell expansion, whether it is involved in adaptive proliferation is largely unknown. First, we report that EGR2 binding to the miR-455 promoter induced miR-455 upregulation in the pancreatic islets of obesity mouse models. Then, in vitro gain- or loss-of-function studies showed that miR-455 overexpression facilitated β-cell proliferation. Knockdown of miR-455 in ob/ob mice via pancreatic intraductal infusion prevented compensatory β-cell expansion. Mechanistically, our results revealed that increased miR-455 expression inhibits the expression of its target cytoplasmic polyadenylation element binding protein 1 (CPEB1), an mRNA binding protein that plays an important role in regulating insulin resistance and cell proliferation. Decreased CPEB1 expression inhibits elongation of the poly-A tail and the subsequent translation of Cdkn1b mRNA, reducing the CDKN1B expression level and finally promoting β-cell proliferation. Taken together, our results show that the miR-455/CPEB1/CDKN1B pathway contributes to adaptive proliferation of β-cells to meet metabolic demand during obesity.

scholarly journals Obesity-Induced miR-455 Upregulation Promotes Adaptive Pancreatic β-cell Proliferation Through the CPEB1/CDKN1B Pathway

2022 ◽  
Author(s):  
Ada Admin ◽  
Qianxing Hu ◽  
Jinming Mu ◽  
Yuhong Liu ◽  
Yue Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Expansion ◽  
Binding Protein ◽  
Pancreatic Β Cell ◽  
Loss Of Function ◽  
Metabolic Demand ◽  
Β Cell ◽  
Element Binding Protein ◽  
Mirna Pathway

Pancreatic β-cell adapt to compensate for increased metabolic demand during obesity. Although the microRNA (miRNA) pathway has an essential role in β-cell expansion, whether it is involved in adaptive proliferation is largely unknown. First, we report that EGR2 binding to the miR-455 promoter induced miR-455 upregulation in the pancreatic islets of obesity mouse models. Then, in vitro gain- or loss-of-function studies showed that miR-455 overexpression facilitated β-cell proliferation. Knockdown of miR-455 in ob/ob mice via pancreatic intraductal infusion prevented compensatory β-cell expansion. Mechanistically, our results revealed that increased miR-455 expression inhibits the expression of its target cytoplasmic polyadenylation element binding protein 1 (CPEB1), an mRNA binding protein that plays an important role in regulating insulin resistance and cell proliferation. Decreased CPEB1 expression inhibits elongation of the poly-A tail and the subsequent translation of Cdkn1b mRNA, reducing the CDKN1B expression level and finally promoting β-cell proliferation. Taken together, our results show that the miR-455/CPEB1/CDKN1B pathway contributes to adaptive proliferation of β-cells to meet metabolic demand during obesity.

scholarly journals A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jennifer Hampton Hill ◽  
Eric A Franzosa ◽  
Curtis Huttenhower ◽  
Karen Guillemin
Keyword(s):  
Cell Proliferation ◽  
Cell Expansion ◽  
Bacterial Species ◽  
Pancreatic Beta Cell ◽  
Fecal Microbiota ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Larval Zebrafish ◽  
Low Diversity ◽  
Early Larval Development

Resident microbes play important roles in the development of the gastrointestinal tract, but their influence on other digestive organs is less well explored. Using the gnotobiotic zebrafish, we discovered that the normal expansion of the pancreatic β cell population during early larval development requires the intestinal microbiota and that specific bacterial members can restore normal β cell numbers. These bacteria share a gene that encodes a previously undescribed protein, named herein BefA (β Cell Expansion Factor A), which is sufficient to induce β cell proliferation in developing zebrafish larvae. Homologs of BefA are present in several human-associated bacterial species, and we show that they have conserved capacity to stimulate β cell proliferation in larval zebrafish. Our findings highlight a role for the microbiota in early pancreatic β cell development and suggest a possible basis for the association between low diversity childhood fecal microbiota and increased diabetes risk.

scholarly journals Silk Fibroin Promotes the Regeneration of Pancreatic β-Cells in the C57BL/KsJ-Leprdb/db Mouse

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3259
Author(s):  
So-young Park ◽  
Boyoung Kim ◽  
Yun Kyung Lee ◽  
Sueun Lee ◽  
Jin Mi Chun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Mouse Model ◽  
Silk Fibroin ◽  
Apoptotic Cell ◽  
Nuclear Antigen ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
In Vivo Models

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic β-cell, we investigated the effects of hydrolyzed SF on the pancreatic β-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic β-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic β-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

scholarly journals Establishment of a pancreatic β cell proliferation model in vitro and a platform for diabetes drug screening

2013 ◽  
Vol 66 (4) ◽  
pp. 687-697 ◽  
Author(s):  
Jing Jia ◽  
Xiaoli Liu ◽  
Yongxia Chen ◽  
Xiaoliang Zheng ◽  
Linglan Tu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Drug Screening ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Diabetes Drug

INCRETIN AND DIABETES

2011 ◽  
pp. 5-10
Author(s):  
Huu Dang Tran
Keyword(s):  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Glycaemic Control ◽  
Animal Studies ◽  
Dipeptidyl Peptidase ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Glucose Sensitivity ◽  
Cell Glucose

The incretins are peptide hormones secreted from the gut in response to food. They increase the secretion of insulin. The incretin response is reduced in patients with type 2 diabetes so drugs acting on incretins may improve glycaemic control. Incretins are metabolised by dipeptidyl peptidase, so selectively inhibiting this enzyme increases the concentration of circulating incretins. A similar effect results from giving an incretin analogue that cannot be cleaved by dipeptidyl peptidase. Studies have identified other actions including improvement in pancreatic β cell glucose sensitivity and, in animal studies, promotion of pancreatic β cell proliferation and reduction in β cell apoptosis.

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