scholarly journals Generation and Characterization of a Novel Mouse Model That Allows Spatiotemporal Quantification of Pancreatic β-Cell Proliferation

Diabetes ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2340-2351 ◽  
Author(s):  
Shinsuke Tokumoto ◽  
Daisuke Yabe ◽  
Hisato Tatsuoka ◽  
Ryota Usui ◽  
Muhammad Fauzi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation

EBioMedicine ◽  
2017 ◽  
Vol 15 ◽  
pp. 163-172 ◽  
Author(s):  
Sohei Tsukita ◽  
Tetsuya Yamada ◽  
Kei Takahashi ◽  
Yuichiro Munakata ◽  
Shinichiro Hosaka ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Generation and characterization of a novel mouse model that allows spatiotemporal quantification of pancreatic β-cell proliferation

2020 ◽  
Author(s):  
Ada Admin ◽  
Shinsuke Tokumoto ◽  
Daisuke Yabe ◽  
Hisato Tatsuoka ◽  
Ryota Usui ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Three Dimensional ◽  
Spatiotemporal Analysis ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Partial Pancreatectomy ◽  
Diet Induced Obesity ◽  
Treatment Of Diabetes

Pancreatic β-cell proliferation has been gaining much attention as a therapeutic target for prevention and treatment of diabetes. In order to evaluate potential β-cell mitogens, accurate and reliable methods for detection and quantification of the β-cell proliferation rate are indispensable. In this study, we developed a novel tool that specifically labels replicating β cells as mVenus<sup>+</sup> cells by using RIP-Cre;R26Fucci2aR mice expressing the fluorescent ubiquitination-based cell cycle indicator Fucci2a in β cells. In response to β-cell proliferation stimuli such as insulin receptor antagonist S961 and diet-induced obesity (DIO), the number of EdU<sup>+</sup> insulin<sup>+ </sup>cells per insulin<sup>+ </sup>cells and the number of mVenus<sup>+ </sup>cells per <a>mCherry<sup>+ </sup>mVenus<sup>-</sup> cells + mCherry<sup>- </sup>mVenus<sup>+</sup> cells</a> were similarly increased in these mice. Three-dimensional imaging of optically cleared pancreas tissue from these mice enabled quantification of replicating β cells in the islets and morphometric analysis of the islets following known mitogenic interventions such as S961, DIO, pregnancy and partial pancreatectomy. Thus, this novel mouse line is a powerful tool for spatiotemporal analysis and quantification of β-cell proliferation in response to mitogenic stimulation.

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 Generation and characterization of a novel mouse model that allows spatiotemporal quantification of pancreatic β-cell proliferation

2020 ◽  
Author(s):  
Ada Admin ◽  
Shinsuke Tokumoto ◽  
Daisuke Yabe ◽  
Hisato Tatsuoka ◽  
Ryota Usui ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Three Dimensional ◽  
Spatiotemporal Analysis ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Partial Pancreatectomy ◽  
Diet Induced Obesity ◽  
Treatment Of Diabetes

Pancreatic β-cell proliferation has been gaining much attention as a therapeutic target for prevention and treatment of diabetes. In order to evaluate potential β-cell mitogens, accurate and reliable methods for detection and quantification of the β-cell proliferation rate are indispensable. In this study, we developed a novel tool that specifically labels replicating β cells as mVenus<sup>+</sup> cells by using RIP-Cre;R26Fucci2aR mice expressing the fluorescent ubiquitination-based cell cycle indicator Fucci2a in β cells. In response to β-cell proliferation stimuli such as insulin receptor antagonist S961 and diet-induced obesity (DIO), the number of EdU<sup>+</sup> insulin<sup>+ </sup>cells per insulin<sup>+ </sup>cells and the number of mVenus<sup>+ </sup>cells per <a>mCherry<sup>+ </sup>mVenus<sup>-</sup> cells + mCherry<sup>- </sup>mVenus<sup>+</sup> cells</a> were similarly increased in these mice. Three-dimensional imaging of optically cleared pancreas tissue from these mice enabled quantification of replicating β cells in the islets and morphometric analysis of the islets following known mitogenic interventions such as S961, DIO, pregnancy and partial pancreatectomy. Thus, this novel mouse line is a powerful tool for spatiotemporal analysis and quantification of β-cell proliferation in response to mitogenic stimulation.

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.

scholarly journals Ontology of the apelinergic system in mouse pancreas during pregnancy and relationship with β-cell mass

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Brenda Strutt ◽  
Sandra Szlapinski ◽  
Thineesha Gnaneswaran ◽  
Sarah Donegan ◽  
Jessica Hill ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Glucose Transporter ◽  
Cell Mass ◽  
Elevated Serum ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Transporter 2 ◽  
Glucose Stimulated Insulin Secretion

AbstractThe apelin receptor (Aplnr) and its ligands, Apelin and Apela, contribute to metabolic control. The insulin resistance associated with pregnancy is accommodated by an expansion of pancreatic β-cell mass (BCM) and increased insulin secretion, involving the proliferation of insulin-expressing, glucose transporter 2-low (Ins+Glut2LO) progenitor cells. We examined changes in the apelinergic system during normal mouse pregnancy and in pregnancies complicated by glucose intolerance with reduced BCM. Expression of Aplnr, Apelin and Apela was quantified in Ins+Glut2LO cells isolated from mouse pancreata and found to be significantly higher than in mature β-cells by DNA microarray and qPCR. Apelin was localized to most β-cells by immunohistochemistry although Aplnr was predominantly associated with Ins+Glut2LO cells. Aplnr-staining cells increased three- to four-fold during pregnancy being maximal at gestational days (GD) 9–12 but were significantly reduced in glucose intolerant mice. Apelin-13 increased β-cell proliferation in isolated mouse islets and INS1E cells, but not glucose-stimulated insulin secretion. Glucose intolerant pregnant mice had significantly elevated serum Apelin levels at GD 9 associated with an increased presence of placental IL-6. Placental expression of the apelinergic axis remained unaltered, however. Results show that the apelinergic system is highly expressed in pancreatic β-cell progenitors and may contribute to β-cell proliferation in pregnancy.

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