scholarly journals Assessment of β-Cell Mass and α- and β-Cell Survival and Function by Arginine Stimulation in Human Autologous Islet Recipients

Diabetes ◽  
2014 ◽  
Vol 64 (2) ◽  
pp. 565-572 ◽  
Author(s):  
R. Paul Robertson ◽  
Lindsey D. Bogachus ◽  
Elizabeth Oseid ◽  
Susan Parazzoli ◽  
Mary Elizabeth Patti ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cell Mass ◽  
Β Cell ◽  
And Function

scholarly journals Puerarin Protects Pancreatic β-Cells in Obese Diabetic Mice via Activation of GLP-1R Signaling

2016 ◽  
Vol 30 (3) ◽  
pp. 361-371 ◽  
Author(s):  
Lei Yang ◽  
Dongdong Yao ◽  
Haiyuan Yang ◽  
Yingjie Wei ◽  
Yunru Peng ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cell Survival ◽  
Body Weight Gain ◽  
Cell Mass ◽  
The Body ◽  
Diabetic Mice ◽  
Β Cell ◽  
Beneficial Effects ◽  
Glucagon Like Peptide 1 ◽  
And Function

Abstract Diabetes is characterized by a loss and dysfunction of the β-cell. Glucagon-like peptide 1 receptor (GLP-1R) signaling plays an important role in β-cell survival and function. It is meaningful to identify promising agents from natural products which might activate GLP-1R signaling. In this study, puerarin, a diet isoflavone, was evaluated its beneficial effects on β-cell survival and GLP-1R pathway. We showed that puerarin reduced the body weight gain, normalized blood glucose, and improved glucose tolerance in high-fat diet-induced and db/db diabetic mice. Most importantly, increased β-cell mass and β-cell proliferation but decreased β-cell apoptosis were observed in puerarin-treated diabetic mice as examined by immunostaining of mice pancreatic sections. The protective effect of puerarin on β-cell survival was confirmed in isolated mouse islets treated with high glucose. Further mechanism studies showed that the circulating level of GLP-1 in mice was unaffected by puerarin. However, puerarin enhanced GLP-1R signaling by up-regulating expressions of GLP-1R and pancreatic and duodenal homeobox 1, which subsequently led to protein kinase B (Akt) activation but forkhead box O1 inactivation, and promoted β-cell survival. The protective effect of puerarin was remarkably suppressed by Exendin(9–39), an antagonist of GLP-1R. Our study demonstrated puerarin improved glucose homeostasis in obese diabetic mice and identified a novel role of puerarin in protecting β-cell survival by mechanisms involving activation of GLP-1R signaling and downstream targets.

scholarly journals Puerarin protects pancreatic β-cell survival via PI3K/Akt signaling pathway

2014 ◽  
Vol 53 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Zhipeng Li ◽  
Zhaoshui Shangguan ◽  
Yijie Liu ◽  
Jihua Wang ◽  
Xuejun Li ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cell Mass ◽  
Akt Signaling ◽  
Pancreatic Β Cell ◽  
Diabetic Mice ◽  
Akt Signaling Pathway ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Stimulated Insulin Secretion ◽  
And Function

Pancreatic β-cell loss because of apoptosis is the major cause of type 1 diabetes (T1D) and late stage T2D. Puerarin possesses anti-diabetic properties; whether it acts directly on pancreatic β-cell is not clear. This study was designed to investigate the effects of puerarin on pancreatic β-cell survival and function. Diabetes was induced in male C57BL/6 mice by a single peritoneal injection of streptozotocin (STZ). Pancreatic β-cell survival and function were assessed in diabetic mice by measuring β-cell apoptosis, β-cell mass, pancreatic insulin content, and glucose tolerance, and in cultured islets and clonial MIN6 β-cells by measuring β-cell viability and apoptosis and glucose-stimulated insulin secretion. We found that pre-treatment with puerarin decreased the incidence of STZ-induced diabetes. Puerarin increased pancreatic β-cell mass via β-cell apoptosis inhibition in diabetic mice, and increased serum insulin, whereas it decreased blood glucose levels and improved glucose tolerance. In cultured islets and MIN6 cells, puerarin protected β-cell from cobalt chloride (CoCl2)-induced apoptosis and restored the impaired capacity of glucose-stimulated insulin secretion. Puerarin protection of β-cell survival involved the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In conclusion, puerarin protects pancreatic β-cell function and survival via direct effects on β-cells, and its protection of β-cell survival is mediated by the PI3K/Akt pathway. As a safe natural plant extraction, puerarin might serve as a preventive and/or therapeutic approach for diabetes.

Identification of transcriptional targets during pancreatic growth after partial pancreatectomy and exendin-4 treatment

2006 ◽  
Vol 24 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Diva D. De León ◽  
Cyrus Farzad ◽  
Michael F. Crutchlow ◽  
John Brestelli ◽  
John Tobias ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cell Mass ◽  
Β Cell ◽  
Cell Specification ◽  
Partial Pancreatectomy ◽  
Pancreatic Growth ◽  
Germ Cell Specification ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
And Function

After partial pancreatectomy (Ppx), substantial regeneration of the endocrine and exocrine pancreatic compartments has been shown in adult rodents. Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor agonist that augments endocrine β-cell mass by stimulating neogenesis, proliferation, and cell survival. After Ppx, treatment with Ex-4 ameliorates hyperglycemia by stimulating β-cell mass recovery. We utilized a cDNA microarray approach to identify genes differentially regulated during pancreatic regeneration after Ppx and/or Ex-4 administration. The pancreatic remnant after Ppx showed a large number of differentially regulated genes. In contrast, Ex-4 treatment resulted in a smaller number of differentially regulated genes. Of note, a common subset of genes regulated by Ex-4 and after Ppx was identified, including three members of the mitogenic Reg gene family, Reg2, -3γ, and -3β, as well as fragilis, a gene that maintains pluripotency during germ cell specification, and Serpin b1a, a member of an intracellular protease inhibitor family involved in cell survival. These observations were confirmed by real-time PCR. We determined that Reg3β protein is also induced in the acinar pancreas after Ppx, suggesting a novel role for this factor in pancreatic growth or response to injury. Finally, comparison of transcription factor-binding sites present in the proximal promoters of these genes identified potential common transcription factors that may regulate these genes. Chromatin immunoprecipitation analyses confirmed Reg3γ as a novel transcriptional target of Foxa2 (HNF3β). Our data suggest molecular pathways that may regulate pancreatic growth and offer a unique set of candidate genes to target in the development of therapies aimed at improving pancreatic growth and function.

Downregulation of Fas activity rescues early onset of diabetes in c-KitWv/+ mice

2013 ◽  
Vol 304 (6) ◽  
pp. E557-E565 ◽  
Author(s):  
Zhi-Chao Feng ◽  
Matthew Riopel ◽  
Jinming Li ◽  
Lisa Donnelly ◽  
Rennian Wang
Keyword(s):  
Cell Survival ◽  
Cell Apoptosis ◽  
Fas Ligand ◽  
Cell Function ◽  
Cell Mass ◽  
Β Cell ◽  
Apoptotic Pathway ◽  
Β Cell Function ◽  
And Function

c-Kit and its ligand stem cell factor (SCF) are important for β-cell survival and maturation; meanwhile, interactions between the Fas receptor (Fas) and Fas ligand are capable of triggering β-cell apoptosis. Disruption of c-Kit signaling leads to severe loss of β-cell mass and function with upregulation of Fas expression in c-Kit Wv/+ mouse islets, suggesting that there is a critical balance between c-Kit and Fas activation in β-cells. In the present study, we investigated the interrelationship between c-Kit and Fas activation that mediates β-cell survival and function. We generated double mutant, c-Kit Wv/+ ;Fas lpr/lpr ( Wv −/−), mice to study the physiological and functional role of Fas with respect to β-cell function in c-Kit Wv/+ mice. Isolated islets from these mice and the INS-1 cell line were used. We observed that islets in c-Kit Wv/+ mice showed a significant increase in β-cell apoptosis along with upregulated p53 and Fas expression. These results were verified in vitro in INS-1 cells treated with SCF or c-Kit siRNA combined with a p53 inhibitor and Fas siRNA. In vivo, Wv −/− mice displayed improved β-cell function, with significantly enhanced insulin secretion and increased β-cell mass and proliferation compared with Wv +/+ mice. This improvement was associated with downregulation of the Fas-mediated caspase-dependent apoptotic pathway and upregulation of the cFlip/NF-κB pathway. These findings demonstrate that a balance between the c-Kit and Fas signaling pathways is critical in the regulation of β-cell survival and function.

VMAT2 gene expression and function as it applies to imaging β-cell mass

2007 ◽  
Vol 86 (1) ◽  
pp. 5-16 ◽  
Author(s):  
Paul E. Harris ◽  
Caterina Ferrara ◽  
Pasquale Barba ◽  
Teresa Polito ◽  
Matthew Freeby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Mass ◽  
Β Cell ◽  
And Function

HDAC1 overexpression enhances β-cell proliferation by down-regulating Cdkn1b/p27

2018 ◽  
Vol 475 (24) ◽  
pp. 3997-4010 ◽  
Author(s):  
Carrie Draney ◽  
Matthew C. Austin ◽  
Aaron H. Leifer ◽  
Courtney J. Smith ◽  
Kyle B. Kener ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Survival ◽  
Cell Mass ◽  
Cyclin B1 ◽  
Β Cell ◽  
Histone Deacetylase 1 ◽  
Cell Cycle Inhibitor ◽  
Homeobox Transcription Factor ◽  
Glucose Stimulated Insulin Secretion

The homeobox transcription factor Nkx6.1 is sufficient to increase functional β-cell mass, where functional β-cell mass refers to the combination of β-cell proliferation, glucose-stimulated insulin secretion (GSIS) and β-cell survival. Here, we demonstrate that the histone deacetylase 1 (HDAC1), which is an early target of Nkx6.1, is sufficient to increase functional β-cell mass. We show that HDAC activity is necessary for Nkx6.1-mediated proliferation, and that HDAC1 is sufficient to increase β-cell proliferation in primary rat islets and the INS-1 832/13 β-cell line. The increase in HDAC1-mediated proliferation occurs while maintaining GSIS and increasing β-cell survival in response to apoptotic stimuli. We demonstrate that HDAC1 overexpression results in decreased expression of the cell cycle inhibitor Cdkn1b/p27 which is essential for inhibiting the G1 to S phase transition of the cell cycle. This corresponds with increased expression of key cell cycle activators, such as Cyclin A2, Cyclin B1 and E2F1, which are activated by activation of the Cdk4/Cdk6/Cyclin D holoenzymes due to down-regulation of Cdkn1b/p27. Finally, we demonstrate that overexpression of Cdkn1b/p27 inhibits HDAC1-mediated β-cell proliferation. Our data suggest that HDAC1 is critical for the Nkx6.1-mediated pathway that enhances functional β-cell mass.

scholarly journals Distinct Roles of β-Cell Mass and Function During Type 1 Diabetes Onset and Remission

Diabetes ◽  
2015 ◽  
Vol 64 (6) ◽  
pp. 2148-2160 ◽  
Author(s):  
Helena Chmelova ◽  
Christian M. Cohrs ◽  
Julie A. Chouinard ◽  
Cathleen Petzold ◽  
Matthias Kuhn ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Mass ◽  
Β Cell ◽  
Diabetes Onset ◽  
And Function

scholarly journals Regulator of G protein signaling 2 is a key regulator of pancreatic β-cell mass and function

2017 ◽  
Vol 8 (5) ◽  
pp. e2821-e2821 ◽  
Author(s):  
H Dong ◽  
Y Zhang ◽  
J Wang ◽  
D S Kim ◽  
H Wu ◽  
...  
Keyword(s):  
G Protein ◽  
Cell Mass ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
And Function

scholarly journals Legacy Effect of Foxo1 in Pancreatic Endocrine Progenitors on Adult β-Cell Mass and Function

Diabetes ◽  
2015 ◽  
Vol 64 (8) ◽  
pp. 2868-2879 ◽  
Author(s):  
Shivatra Chutima Talchai ◽  
Domenico Accili
Keyword(s):  
Cell Mass ◽  
Β Cell ◽  
Legacy Effect ◽  
And Function ◽  
Endocrine Progenitors
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