scholarly journals Pancreatic β cell–selective zinc transporter 8 insufficiency accelerates diabetes associated with islet amyloidosis

JCI Insight ◽  
2021 ◽  
Vol 6 (10) ◽  
Author(s):  
Jie Xu ◽  
Nadeeja Wijesekara ◽  
Romario Regeenes ◽  
Dana Al Rijjal ◽  
Anthony L. Piro ◽  
...  
Keyword(s):  
Zinc Transporter ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Zinc Transporter 8

scholarly journals Acute cytokine-mediated downregulation of the zinc transporter ZnT8 alters pancreatic β-cell function

2010 ◽  
Vol 206 (3) ◽  
pp. 336
Author(s):  
Malek El Muayed ◽  
Liana K Billings ◽  
Meera R Raja ◽  
Xiaomin Zhang ◽  
Paul J Park ◽  
...  
Keyword(s):  
Cell Function ◽  
Zinc Transporter ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Zinc transporter 8 (ZnT8) and β cell function

2014 ◽  
Vol 25 (8) ◽  
pp. 415-424 ◽  
Author(s):  
Howard W. Davidson ◽  
Janet M. Wenzlau ◽  
Richard M. O’Brien
Keyword(s):  
Cell Function ◽  
Zinc Transporter ◽  
Β Cell ◽  
Zinc Transporter 8 ◽  
Β Cell Function

scholarly journals Characterization of zinc transporter 8 (ZnT8) antibodies in autoimmune diabetic patients from Argentinian population using monomeric, homodimeric, and heterodimeric ZnT8 antigen variants

2016 ◽  
Vol 174 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Natalia I Faccinetti ◽  
Luciano L Guerra ◽  
Alberto Penas Steinhardt ◽  
Ruben F Iacono ◽  
Gustavo D Frechtel ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Zinc Transporter ◽  
Actual State ◽  
Diabetic Patients ◽  
Obese Adult ◽  
Adult Onset ◽  
Β Cell ◽  
Zinc Transporter 8 ◽  
Type 1 Diabetic Patients

ObjectiveIn order to gain further knowledge of the structure of zinc transporter 8 (ZnT8) epitopes, we studied the role of the amino acid at position 325 in the antigen and its dimeric conformation for autoantibodies to ZnT8 (ZnT8A) recognition.MethodsFor this purpose, several ZnT8 C-terminal domain variants were designed: monomer carrying Arg325 or Trp325, homo-dimers ZnT8-Arg–Arg325 and ZnT8-Trp–Trp325, and hetero-dimer ZnT8-Arg–Trp325. Two groups of Argentinian diabetic patients were subjected to analysis using [35S]-ZnT8 variants by radioligand binding assay (RBA): i) 100 new-onset, insulin-dependent, type 1 diabetic patients and ii) 282 slowly progressing to insulin requirement, non-obese adult-onset diabetic patients. In addition, 50 type 1 diabetic patients and 100 normal control sera provided by the American Diabetes Association (ADA) were evaluated in order to calculate the sensitivity and specificity of ZnT8A assays for each antigenic variant. Other routine β-cell autoantibodies were also tested by RBA.ResultsOf the 100 Argentinian type 1 diabetic patients, 65 were ZnT8A+. Out of them, 8 patients recognized all recombinant forms of ZnT8 and most patients (56) reacted against the heterodimer. Additionally, out of 282 non-obese adult-onset diabetic patients 46 were ZnT8A+, whereas 29 patients recognized only dimers. Besides, exclusive reactivity against ZnT8A was found in 9.0% for type 1 diabetes mellitus and 10.3% for non-obese adult-onset diabetic patients.ConclusionsSignificantly higher signal values in RBA were obtained with the heterodimeric variant. An increased detection of humoral autoimmunity was found in both groups when ZnT8A was employed in combination with the other β-cell autoantibodies. The inclusion of homodimeric immunoreactive peptides revealed the existence of quaternary structure-defined epitopes probably resembling the actual state of the autoantigenin vivo. Finally, the differential profiles of ZnT8A exhibited by type 1 and non-obese adult-onset diabetic patients suggest the different nature of autoimmune processes underlying both pathologies.

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo
Keyword(s):  
Metabolic Diseases ◽  
Cell Function ◽  
Whole Body ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Axis ◽  
Β Cell Function ◽  
Prevalence Of Obesity ◽  
Specific Factors ◽  
Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

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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