scholarly journals Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes

2019 ◽  
Vol 19 (9) ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Alexandra E. Butler
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Identity

scholarly journals Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 395-409 ◽  
Author(s):  
Masaya Oshima ◽  
Séverine Pechberty ◽  
Lara Bellini ◽  
Sven O. Göpel ◽  
Mélanie Campana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Identity ◽  
Human Beta Cells ◽  
Human Beta Cell ◽  
Stearoyl Coa Desaturase

Abstract Aims/hypothesis During the onset of type 2 diabetes, excessive dietary intake of saturated NEFA and fructose lead to impaired insulin production and secretion by insulin-producing pancreatic beta cells. The majority of data on the deleterious effects of lipids on functional beta cell mass were obtained either in vivo in rodent models or in vitro using rodent islets and beta cell lines. Translating data from rodent to human beta cells remains challenging. Here, we used the human beta cell line EndoC-βH1 and analysed its sensitivity to a lipotoxic and glucolipotoxic (high palmitate with or without high glucose) insult, as a way to model human beta cells in a type 2 diabetes environment. Methods EndoC-βH1 cells were exposed to palmitate after knockdown of genes related to saturated NEFA metabolism. We analysed whether and how palmitate induces apoptosis, stress and inflammation and modulates beta cell identity. Results EndoC-βH1 cells were insensitive to the deleterious effects of saturated NEFA (palmitate and stearate) unless stearoyl CoA desaturase (SCD) was silenced. SCD was abundantly expressed in EndoC-βH1 cells, as well as in human islets and human induced pluripotent stem cell-derived beta cells. SCD silencing induced markers of inflammation and endoplasmic reticulum stress and also IAPP mRNA. Treatment with the SCD products oleate or palmitoleate reversed inflammation and endoplasmic reticulum stress. Upon SCD knockdown, palmitate induced expression of dedifferentiation markers such as SOX9, MYC and HES1. Interestingly, SCD knockdown by itself disrupted beta cell identity with a decrease in mature beta cell markers INS, MAFA and SLC30A8 and decreased insulin content and glucose-stimulated insulin secretion. Conclusions/interpretation The present study delineates an important role for SCD in the protection against lipotoxicity and in the maintenance of human beta cell identity. Data availability Microarray data and all experimental details that support the findings of this study have been deposited in in the GEO database with the GSE130208 accession code.

scholarly journals The central role of calcium in the effects of cytokines on beta-cell function: Implications for type 1 and type 2 diabetes

Cell Calcium ◽  
2011 ◽  
Vol 50 (6) ◽  
pp. 481-490 ◽  
Author(s):  
James W. Ramadan ◽  
Stephen R. Steiner ◽  
Christina M. O’Neill ◽  
Craig S. Nunemaker
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function

scholarly journals GLIS3, a Susceptibility Gene for Type 1 and Type 2 Diabetes, Modulates Pancreatic Beta Cell Apoptosis via Regulation of a Splice Variant of the BH3-Only Protein Bim

PLoS Genetics ◽  
2013 ◽  
Vol 9 (5) ◽  
pp. e1003532 ◽  
Author(s):  
Tatiane C. Nogueira ◽  
Flavia M. Paula ◽  
Olatz Villate ◽  
Maikel L. Colli ◽  
Rodrigo F. Moura ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Apoptosis ◽  
Splice Variant ◽  
Pancreatic Beta Cell ◽  
Susceptibility Gene ◽  
Beta Cell Apoptosis

PS18 - 3. Loss of beta-cell identity occurs in type 2 diabetes and is associated with islet amyloid depositions

2013 ◽  
Vol 11 (4) ◽  
pp. 201-201
Author(s):  
H. Siebe Spijker ◽  
Heein Song ◽  
Anne Clark ◽  
Marten Engelse ◽  
Ton J. Rabelink ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Islet Amyloid ◽  
Cell Identity

scholarly journals Next steps in the identification of gene targets for type 1 diabetes

Diabetologia ◽  
2020 ◽  
Vol 63 (11) ◽  
pp. 2260-2269 ◽  
Author(s):  
Struan F. A. Grant ◽  
Andrew D. Wells ◽  
Stephen S. Rich
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Cell Types ◽  
Total Risk ◽  
Chromosome Conformation

Abstract The purpose of this review is to provide a view of the future of genomics and other omics approaches in defining the genetic contribution to all stages of risk of type 1 diabetes and the functional impact and clinical implementations of the associated variants. From the recognition nearly 50 years ago that genetics (in the form of HLA) distinguishes risk of type 1 diabetes from type 2 diabetes, advances in technology and sample acquisition through collaboration have identified over 60 loci harbouring SNPs associated with type 1 diabetes risk. Coupled with HLA region genes, these variants account for the majority of the genetic risk (~50% of the total risk); however, relatively few variants are located in coding regions of genes exerting a predicted protein change. The vast majority of genetic risk in type 1 diabetes appears to be attributed to regions of the genome involved in gene regulation, but the target effectors of those genetic variants are not readily identifiable. Although past genetic studies clearly implicated immune-relevant cell types involved in risk, the target organ (the beta cell) was left untouched. Through emergent technologies, using combinations of genetics, gene expression, epigenetics, chromosome conformation and gene editing, novel landscapes of how SNPs regulate genes have emerged. Furthermore, both the immune system and the beta cell and their biological pathways have been implicated in a context-specific manner. The use of variants from immune and beta cell studies distinguish type 1 diabetes from type 2 diabetes and, when they are combined in a genetic risk score, open new avenues for prediction and treatment.

scholarly journals Oral administration of bacterial Beta cell expansion factor A (BefA) alleviates diabetes in mice with Type 1 and Type 2 diabetes

2021 ◽  
Author(s):  
Huan Wang ◽  
Jing Wei ◽  
Hong Hu ◽  
Fuyin Le ◽  
Heng Wu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Expansion ◽  
Dependent Manner ◽  
Expansion Factor ◽  
Concentration Dependent Manner ◽  
Protective Function

Diabetes mellitus (DM) is a group of metabolic diseases, which is of urgent need to develop new therapeutic DM oral drugs with less side effects and sound therapeutic efficacy. In this study, a Beta cell expansion factor A (BefA) production strain of Escherichia Coli BL21-pet 28C-BefA was constructed, and the anti-diabetes effect of BefAwas evaluated using type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mice models. The T1DM mice results indicated that BefA significantly reduced the blood glucose level, exerted protective function of islet β cell morphology, down-regulated the TLR-4, p-NFκB/NFκB, Bax/Bcl-2 expressions and the secretion level of IL-1β, TNF-α, increased the expression of PDX-1 protein and insulin secretion in a concentration-dependent manner, and restored the disturbed microbial diversity to normal level. Similar with the T1DM mice, BefA obviously increased islet β cells, reduced inflammatory reaction and apoptosis in T2DM mice, and also improved liver lipid metabolism by down-regulating the expression of CEBP-α, ACC, Fasn and inhibiting the synthesis of triglyceride and induce Cpt-1, Hmgcs2, Pparα in a concentration-dependent manner. In the present study, we verified therapeutic effect and potential mechanisms of BefA in mammal for the first time, providing basic data for its clinical application.

scholarly journals Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes

2016 ◽  
Vol 48 (5) ◽  
pp. 519-527 ◽  
Author(s):  
James Dooley ◽  
Lei Tian ◽  
Susann Schonefeldt ◽  
Viviane Delghingaro-Augusto ◽  
Josselyn E Garcia-Perez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Genetic Predisposition
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