scholarly journals Angiotension II induced insulin resistance and mitochondrial disruption are diminished in p47phox deficient mice

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Craig Stump ◽  
Guanjie Chen ◽  
Allyson Booth ◽  
Maggie Diamond‐Stanic ◽  
Erik Henriksen
Keyword(s):  
Insulin Resistance ◽  
Angiotension Ii ◽  
Mitochondrial Disruption ◽  
Deficient Mice

Reduced bone formation and increased adiposity with insulin resistance in interleukin-11 deficient mice

2014 ◽  
Author(s):  
Bingzi Dong ◽  
Takeshi Kondo ◽  
Yukiyo Ohnishi ◽  
Itsuro Endo ◽  
Masahiro Abe ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Formation ◽  
Interleukin 11 ◽  
Deficient Mice

scholarly journals 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

2012 ◽  
Vol 302 (6) ◽  
pp. E654-E665 ◽  
Author(s):  
Banumathi K. Cole ◽  
Norine S. Kuhn ◽  
Shamina M. Green-Mitchell ◽  
Kendall A. Leone ◽  
Rebekah M. Raab ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Stress Markers ◽  
Deficient Mice

Central obesity is associated with chronic inflammation, insulin resistance, β-cell dysfunction, and endoplasmic reticulum (ER) stress. The 12/15-lipoxygenase enzyme (12/15-LO) promotes inflammation and insulin resistance in adipose and peripheral tissues. Given that obesity is associated with ER stress and 12/15-LO is expressed in adipose tissue, we determined whether 12/15-LO could mediate ER stress signals. Addition of 12/15-LO lipid products 12(S)-HETE and 12(S)-HPETE to differentiated 3T3-L1 adipocytes induced expression and activation of ER stress markers, including BiP, XBP-1, p-PERK, and p-IRE1α. The ER stress inducer, tunicamycin, upregulated ER stress markers in adipocytes with concomitant 12/15-LO activation. Addition of a 12/15-LO inhibitor, CDC, to tunicamycin-treated adipocytes attenuated the ER stress response. Furthermore, 12/15-LO-deficient adipocytes exhibited significantly decreased tunicamycin-induced ER stress. 12/15-LO action involves upregulation of interleukin-12 (IL-12) expression. Tunicamycin significantly upregulated IL-12p40 expression in adipocytes, and IL-12 addition increased ER stress gene expression; conversely, LSF, an IL-12 signaling inhibitor, and an IL-12p40-neutralizing antibody attenuated tunicamycin-induced ER stress. Isolated adipocytes and liver from 12/15-LO-deficient mice fed a high-fat diet revealed a decrease in spliced XBP-1 expression compared with wild-type C57BL/6 mice on a high-fat diet. Furthermore, pancreatic islets from 12/15-LO-deficient mice showed reduced high-fat diet-induced ER stress genes compared with wild-type mice. These data suggest that 12/15-LO activity participates in ER stress in adipocytes, pancreatic islets, and liver. Therefore, reduction of 12/15-LO activity or expression could provide a new therapeutic target to reduce ER stress and downstream inflammation linked to obesity.

scholarly journals Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2109-2117 ◽  
Author(s):  
Elodie Riant ◽  
Aurélie Waget ◽  
Haude Cogo ◽  
Jean-François Arnal ◽  
Rémy Burcelin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Normal Chow ◽  
Visceral Adipose ◽  
Deficient Mice ◽  
Normal Chow Diet

Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor α (ERα), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17β-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERα-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-α) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERα-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERα pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.

Disruption of endothelial Pfkfb3 ameliorates diet-induced murine insulin resistance

2021 ◽  
Author(s):  
Qiuhua Yang ◽  
Jiean Xu ◽  
Qian Ma ◽  
Zhiping Liu ◽  
Yaqi Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Cells ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Endothelial Inflammation ◽  
Glucose Clearance ◽  
Deficient Mice

Overnutrition-induced endothelial inflammation plays a crucial role in high fat diet (HFD)-induced insulin resistance in animals. Endothelial glycolysis plays a critical role in endothelial inflammation and proliferation, but its role in diet-induced endothelial inflammation and subsequent insulin resistance has not been elucidated. PFKFB3 is a critical glycolytic regulator, and its increased expression has been observed in adipose vascular endothelium of C57BL/6J mice fed with HFD in vivo, and in palmitate (PA)-treated primary human adipose microvascular endothelial cells (HAMECs) in vitro. We generated mice with Pfkfb3 deficiency selective for endothelial cells to examine the effect of endothelial Pfkfb3 in endothelial inflammation in metabolic organs and in the development of HFD-induced insulin resistance. EC Pfkfb3-deficient mice exhibited mitigated HFD-induced insulin resistance, including decreased body weight and fat mass, improved glucose clearance and insulin sensitivity, and alleviated adiposity and hepatic steatosis. Mechanistically, cultured PFKFB3 knockdown HAMECs showed decreased NF-κB activation induced by PA, and consequent suppressed adhesion molecule expression and monocyte adhesion. Taken together, these results demonstrate that increased endothelial PFKFB3 expression promotes diet-induced inflammatory responses and subsequent insulin resistance, suggesting that endothelial metabolic alteration plays an important role in the development of insulin resistance.

scholarly journals CXCL12-CXCR4 pathway activates brown adipocytes and induces insulin resistance in CXCR4-deficient mice under high-fat diet

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kenichi Kurita ◽  
Ko Ishikawa ◽  
Kenji Takeda ◽  
Masanori Fujimoto ◽  
Hiraku Ono ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
High Fat ◽  
Brown Adipocytes ◽  
Deficient Mice

scholarly journals Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine

Oncotarget ◽  
2017 ◽  
Vol 8 (38) ◽  
pp. 63281-63289 ◽  
Author(s):  
Zhao-Hui Cui ◽  
Qi Yuan ◽  
Li Mao ◽  
Feng-Li Chen ◽  
Feng Ji ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Deficient Mice

scholarly journals Angiotensin II-Induced Insulin Resistance Is Enhanced in Adrenomedullin-Deficient Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3647-3651 ◽  
Author(s):  
Guangqun Xing ◽  
Tatsuo Shimosawa ◽  
Takehide Ogihara ◽  
Hiromitsu Matsui ◽  
Kanami Itakura ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Deficient Mice

scholarly journals Nuclear Orphan Receptor TAK1/TR4-Deficient Mice Are Protected Against Obesity-Linked Inflammation, Hepatic Steatosis, and Insulin Resistance

Diabetes ◽  
2010 ◽  
Vol 60 (1) ◽  
pp. 177-188 ◽  
Author(s):  
Hong Soon Kang ◽  
Kyoko Okamoto ◽  
Yong-Sik Kim ◽  
Yukimasa Takeda ◽  
Carl D. Bortner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Orphan Receptor ◽  
Nuclear Orphan Receptor ◽  
Deficient Mice

scholarly journals B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues

2020 ◽  
Vol 21 (14) ◽  
pp. 5121
Author(s):  
Bobae Kim ◽  
Chang-Kee Hyun
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
B Cell ◽  
Adipose Tissues ◽  
B Cell Activating Factor ◽  
Proliferation And Differentiation ◽  
Regulated Expression ◽  
Cold Challenge ◽  
Subcutaneous Adipose ◽  
Deficient Mice

Impaired glucose tolerance is a common feature associated with human aging, which is caused by defects in insulin secretion, insulin action or both. Recent studies have suggested that B-cell-activating factor (BAFF), a cytokine that modulates proliferation and differentiation of B cells, and its receptors are expressed in mature adipocytes and preadipocytes, proposing BAFF as a potential regulator of energy metabolism. In this study, we show that systemic BAFF depletion improves aging-dependent insulin resistance. In aged (10-month-old) BAFF−/− mice, glucose tolerance and insulin sensitivity were significantly improved despite higher adiposity as a result of expansion of adipose tissues compared to wild-type controls. BAFF−/− mice displayed an improved response to acute cold challenge, commensurate with the up-regulated expression of thermogenic genes in both brown and subcutaneous adipose tissues. These changes were found to be mediated by both increased M2-like (alternative) macrophage activation and enhanced leptin and FGF21 production, which may account for the improving effect of BAFF depletion on insulin resistance. In addition, leptin-deficient mice (ob/ob) showed augmented BAFF signaling concomitant with impaired thermogenic activity, identifying BAFF as a suppressive factor to thermogenesis. Our findings suggest that suppression of BAFF could be a therapeutic approach to attenuate aging-dependent insulin resistance.

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