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

Interleukin 10 inhibits insulin release from and nitric oxide production in rat pancreatic islets

1996 ◽  
Vol 135 (3) ◽  
pp. 374-378 ◽  
Author(s):  
Renato Laffranchi ◽  
Giatgen A Spinas
Keyword(s):  
Nitric Oxide ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Interleukin 10 ◽  
Interleukin 1Β ◽  
Nitric Oxide Production ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Rat Pancreatic Islets ◽  
Oxide Production

Laffranchi R, Spinas GA. Interleukin 10 inhibits insulin release from and nitric oxide production in rat pancreatic islets. Eur J Endocrinol 1996;135:374–8. ISSN 0804–4643 Interleukin 10 was found to prevent cytokine-induced nitric oxide production in murine macrophages. Because, in rat islets, interleukin 1β induces β-cell dysfunction, mainly due to overproduction of nitric oxide, we studied if this effect could be counteracted by interleukin 10. Rat pancreatic islets were cultured for 24 h in the presence or absence of 0.02–20 ng/ml recombinant human interleukin 10. Interleukin 10 dose-dependently inhibited insulin secretion with maximal inhibition (27 ±4%, p < 0.05) at 2 ng/ml without impairment of islet cell viability. However, incubation of pancreatic islets with interleukin 10 resulted in a 61.5% decrease of nitric oxide production. Co-incubation of islets with interleukin 10 (2 ng/ml) and recombinant human interleukin 1β (0.15 ng/ml) resulted in a more pronounced suppression of basal insulin release than with interleukin 1β alone (55 ± 3.6% vs 44 ± 3.6% with interleukin 1β alone, p < 0.05) but did not reduce interleukin 1β-stimulated NO production or reverse the effect of interleukin 1β on cell viability. Thus, in pancreatic islets interleukin 10 is not capable of counteracting the interleukin 1β-induced β-cell dysfunction, but rather enhances the inhibitory effect of interleukin 1β by a different mechanism. Renato Laffranchi, Division of Endocrinology and Metabolism, Department of Internal Medicine, University Hospital, Rämistrasse 100, CH-8091 Zürich, Switzerland

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

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 Causes β-Cell Dysfunction Through an ER Stress-Induced Proinflammatory Response

Endocrinology ◽  
2017 ◽  
Vol 158 (10) ◽  
pp. 3162-3173 ◽  
Author(s):  
Stanley M H Chan ◽  
Yeh-Siang Lau ◽  
Alyson A Miller ◽  
Jacqueline M Ku ◽  
Simon Potocnik ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Er Stress ◽  
Β Cell ◽  
Proinflammatory Response ◽  
Cell Dysfunction

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.

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.

scholarly journals RIPK3-mediated inflammation is a conserved β cell response to ER stress

2020 ◽  
Vol 6 (51) ◽  
pp. eabd7272
Author(s):  
Bingyuan Yang ◽  
Lisette A. Maddison ◽  
Karolina E. Zaborska ◽  
Chunhua Dai ◽  
Linlin Yin ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Response ◽  
Dependent Manner ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Proinflammatory Mediators ◽  
Islet Inflammation

Islet inflammation is an important etiopathology of type 2 diabetes; however, the underlying mechanisms are not well defined. Using complementary experimental models, we discovered RIPK3-dependent IL1B induction in β cells as an instigator of islet inflammation. In cultured β cells, ER stress activated RIPK3, leading to NF-kB–mediated proinflammatory gene expression. In a zebrafish muscle insulin resistance model, overnutrition caused islet inflammation, β cell dysfunction, and loss in an ER stress–, ripk3-, and il1b-dependent manner. In mouse islets, high-fat diet triggered the IL1B expression in β cells before macrophage recruitment in vivo, and RIPK3 inhibition suppressed palmitate-induced β cell dysfunction and Il1b expression in vitro. Furthermore, in human islets grafted in hyperglycemic mice, a marked increase in ER stress, RIPK3, and NF-kB activation in β cells were accompanied with murine macrophage infiltration. Thus, RIPK3-mediated induction of proinflammatory mediators is a conserved, previously unrecognized β cell response to metabolic stress and a mediator of the ensuing islet inflammation.

GPR120 protects lipotoxicity-induced pancreatic β-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation

2019 ◽  
Vol 133 (1) ◽  
pp. 101-116 ◽  
Author(s):  
Yi Wang ◽  
Ting Xie ◽  
Dan Zhang ◽  
Po Sing Leung
Keyword(s):  
Signaling Pathways ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Min6 Cells ◽  
Cell Dysfunction ◽  
Obesity And Diabetes ◽  
Β Cell Function ◽  
Islet Inflammation ◽  
Pdx1 Expression

Abstract G-protein coupled receptor 120 (GPR120) has been shown to act as an omega-3 unsaturated fatty acid sensor and is involved in insulin secretion. However, the underlying mechanism in pancreatic β cells remains unclear. To explore the potential link between GPR120 and β-cell function, its agonists docosahexaenoic acid (DHA) and GSK137647A were used in palmitic acid (PA)-induced pancreatic β-cell dysfunction, coupled with GPR120 knockdown (KD) in MIN6 cells and GPR120 knockout (KO) mice to identify the underlying signaling pathways. In vitro and ex vivo treatments of MIN6 cells and islets isolated from wild-type (WT) mice with DHA and GSK137647A restored pancreatic duodenal homeobox-1 (PDX1) expression levels and β-cell function via inhibiting PA-induced elevation of proinflammatory chemokines and activation of nuclear factor κB, c-Jun amino (N)-terminal kinases1/2 and p38MAPK signaling pathways. On the contrary, these GPR120 agonism-mediated protective effects were abolished in GPR120 KD cells and islets isolated from GPR120 KO mice. Furthermore, GPR120 KO mice displayed glucose intolerance and insulin resistance relative to WT littermates, and β-cell functional related genes were decreased while inflammation was exacerbated in islets with increased macrophages in pancreas from GPR120 KO mice. DHA and GSK137647A supplementation ameliorated glucose tolerance and insulin sensitivity, as well as improved Pdx1 expression and islet inflammation in diet-induced obese WT mice, but not in GPR120 KO mice. These findings indicate that GPR120 activation is protective against lipotoxicity-induced pancreatic β-cell dysfunction, via the mediation of PDX1 expression and inhibition of islet inflammation, and that GPR120 activation may serve as a preventative and therapeutic target for obesity and diabetes.

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