scholarly journals Saturated Fatty Acid and TLR Signaling Link β Cell Dysfunction and Islet Inflammation

2012 ◽  
Vol 15 (4) ◽  
pp. 518-533 ◽  
Author(s):  
Kosei Eguchi ◽  
Ichiro Manabe ◽  
Yumiko Oishi-Tanaka ◽  
Mitsuru Ohsugi ◽  
Nozomu Kono ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Β Cell ◽  
Tlr Signaling ◽  
Cell Dysfunction ◽  
Islet Inflammation

scholarly journals Susceptibility to Fatty Acid-Induced β-Cell Dysfunction Is Enhanced in Prediabetic Diabetes-Prone BioBreeding Rats: A Potential Link Between β-Cell Lipotoxicity and Islet Inflammation

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 89-101 ◽  
Author(s):  
Christine Tang ◽  
Anthony E. Naassan ◽  
Astrid Chamson-Reig ◽  
Khajag Koulajian ◽  
Tracy T. Goh ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Fatty Acid ◽  
Cell Function ◽  
Ex Vivo ◽  
Autoimmune Diabetes ◽  
Bb Rat ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Islet Inflammation

β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity may be synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ∼2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo. IH significantly decreased β-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine. Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats. In conclusion, the presence of insulitis was permissive for IH-induced β-cell dysfunction in the BB rat, which suggests a link between β-cell lipotoxicity and islet inflammation.

High-throughput screening and bioinformatic analysis to ascertain compounds that prevent saturated fatty acid-induced β-cell apoptosis

2017 ◽  
Vol 138 ◽  
pp. 140-149 ◽  
Author(s):  
Seung-Hee Lee ◽  
Daniel Cunha ◽  
Carlo Piermarocchi ◽  
Giovanni Paternostro ◽  
Anthony Pinkerton ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
High Throughput ◽  
Cell Apoptosis ◽  
High Throughput Screening ◽  
Bioinformatic Analysis ◽  
Β Cell

scholarly journals Peroxisome Deficiency Dysregulates Fatty Acid Oxidization and Exacerbates Lipotoxicity in β Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hongbo Guan ◽  
Yanyan Guo ◽  
Liangliang Zhu ◽  
Yisheng Jiao ◽  
Xiaomei Liu
Keyword(s):  
Fatty Acid ◽  
Inflammatory Responses ◽  
Cell Mass ◽  
Vital Role ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Peroxisomal Biogenesis ◽  
Wide Range ◽  
The Impact

An adverse intrauterine environment impairs the development of pancreatic islets in the fetus and leads to insufficient β cell mass and β cell dysfunction. We previously reported that Pex14, a peroxin protein involved in the biogenesis and degradation of peroxisomes, is markedly reduced in the pancreas of an intrauterine growth restriction fetus and last into adulthood. Peroxisomes function in a wide range of metabolic processes including fatty acid oxidization, ROS detoxification, and anti-inflammatory responses. To elucidate the impact of downregulation of the Pex14 gene on β cell, Pex14 was knocked down by siRNA in INS-1 cells. Pex14 knockdown disturbed peroxisomal biogenesis and dysregulated fatty acid metabolism and lipid storage capability, thereby increased ROS level and blunted insulin secretion. Moreover, Pex14 knockdown upregulated inflammation factors and regulators of endoplasmic reticulum stress. The lipotoxicity of fatty acid (including palmitic acid and linoleic acid) in β cells was exacerbated by knockdown of Pex14, as indicated by H2O2 accumulation and increased programmed cell death. The present results demonstrate the vital role of Pex14 in maintaining normal peroxisome function and β cell viability and highlight the importance of a functional peroxisomal metabolism for the detoxification of excess FAs in β cells.

Islet Inflammation in Type 2 Diabetes (T2D): From Endothelial to β-Cell Dysfunction

2007 ◽  
Vol 3 (3) ◽  
pp. 216-232 ◽  
Author(s):  
Jan A. Ehses ◽  
Sophie Calderari ◽  
Jean-Claude Irminger ◽  
Patricia Serradas ◽  
Marie-Helene Giroix ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Islet Inflammation

scholarly journals The Furan Fatty Acid Metabolite CMPF Is Elevated in Diabetes and Induces β Cell Dysfunction

2014 ◽  
Vol 19 (4) ◽  
pp. 653-666 ◽  
Author(s):  
Kacey J. Prentice ◽  
Lemieux Luu ◽  
Emma M. Allister ◽  
Ying Liu ◽  
Lucy S. Jun ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Acid Metabolite ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Fatty Acid Metabolite ◽  
Furan Fatty Acid

T-Helper Cell–Mediated Islet Inflammation Contributes to β-Cell Dysfunction in Chronic Pancreatitis

Pancreas ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 434-442 ◽  
Author(s):  
Rupjyoti Talukdar ◽  
Mitnala Sasikala ◽  
Pondugala Pavan Kumar ◽  
Guduru Venkata Rao ◽  
Rebala Pradeep ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Islet Inflammation

scholarly journals Amyloid‐induced β‐cell dysfunction and islet inflammation are ameliorated by 4‐phenylbutyrate (PBA) treatment

2017 ◽  
Vol 31 (12) ◽  
pp. 5296-5306 ◽  
Author(s):  
Joel Montane ◽  
Sara Pablo ◽  
Carlos Castaño ◽  
Júlia Rodríguez‐Comas ◽  
Lisa Cadavez ◽  
...  
Keyword(s):  
Β Cell ◽  
Cell Dysfunction ◽  
Islet Inflammation

scholarly journals Angiotensin II Induces Interleukin-1β–Mediated Islet Inflammation and β-Cell Dysfunction Independently of Vasoconstrictive Effects

Diabetes ◽  
2014 ◽  
Vol 64 (4) ◽  
pp. 1273-1283 ◽  
Author(s):  
Nadine S. Sauter ◽  
Constanze Thienel ◽  
Yuliya Plutino ◽  
Kapil Kampe ◽  
Erez Dror ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Interleukin 1Β ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Islet Inflammation

scholarly journals Oleic Acid Protected Pancreatic β‐Cell Against Saturated Fatty Acid Induced Lipotoxicity

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Xiaohong Liu ◽  
Xuanming Chen ◽  
Linzhao Li ◽  
Ruixi Luo ◽  
Dan Long ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Fetuin-A secretion from β-cell accumulates macrophages in islets, aggravates inflammation and impairs insulin secretion

2021 ◽  
Author(s):  
Alpana Mukhuty ◽  
Chandrani Fouzder ◽  
Rakesh Kundu
Keyword(s):  
Insulin Secretion ◽  
Macrophage Polarization ◽  
Boyden Chamber ◽  
Β Cell ◽  
Fetuin A ◽  
Cell Dysfunction ◽  
Insulinoma Cell ◽  
Islet Inflammation ◽  
Inflammatory Macrophages ◽  
M1 Type

Elevated fetuin-A levels, chemokines and islet resident macrophages are crucial factors associated with obesity mediated Type 2 Diabetes (T2D). Here, the aim of the study was to investigate the effect of MIN6 (mouse insulinoma cell line) derived fetuin-A in macrophage polarization and decipher the effect of M1 type pro-inflammatory macrophages in commanding over insulin secretion. MIN6 and islet derived fetuin-A induced expression of M1 type macrophage markers, Emr1, Cd68 and CD11c (∼1.8 fold) along with increased cytokine secretion. Interestingly, suppression of fetuin-A in MIN6 successfully reduced M1 markers by ∼1.5 fold. MIN6 derived fetuin-A also induced chemotaxis of macrophages in Boyden chamber chemotaxis assay. Further, high fat feeding in mice showed elevated cytokine and fetuin-A content in serum and islets, and also migration and polarization of macrophages to the islets while β-cells failed to cope up with increased insulin demand. Moreover, in MIN6 culture, M1 macrophages sharply decreased insulin secretion by ∼2.8 fold. Altogether our results support an association of fetuin-A with islet inflammation and β-cell dysfunction, owing to its role as a key chemoattractant and macrophage polarizing factor.

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