Tu-P7:187 NF-KB in a genetic model of insulin resistance and postprandial lipemia

2006 ◽  
Vol 7 (3) ◽  
pp. 226
Author(s):  
S. Martinez-Hervas ◽  
T. Pedro ◽  
J.T. Real ◽  
A. Bartual ◽  
F.J. Chaves ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Genetic Model ◽  
Postprandial Lipemia

scholarly journals EET Analog Treatment Improves Insulin Signaling in a Genetic Mouse Model of Insulin Resistance

2021 ◽  
Author(s):  
Kakali Ghoshal ◽  
Xiyue Li ◽  
Dungeng Peng ◽  
John R. Falck ◽  
Raghunath Reddy Anugu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Signaling ◽  
Genetic Model ◽  
Water Soluble ◽  
Hepatic Insulin Resistance ◽  
Epoxyeicosatrienoic Acid ◽  
Genetic Mouse Model ◽  
Hepatic Insulin Signaling ◽  
Underlying Mechanisms

We previously showed that global deletion of the cytochrome P450 epoxygenase <i>Cyp2c44</i>, a major epoxyeicosatrienoic acid (EET) producing enzyme in mice, leads to impaired hepatic insulin signaling resulting in insulin resistance. This finding led us to investigate whether administration of a water soluble EET analog restores insulin signaling <i>in vivo</i> in <i>Cyp2c44(-/-)</i> mice and investigated the underlying mechanisms by which this effect is exerted. <i>Cyp2c44(-/-)</i> mice treated with the analog EET-A for 4 weeks improved fasting glucose and glucose tolerance compared to <i>Cyp2c44(-/-)</i> mice treated with vehicle alone. This beneficial effect was accompanied by enhanced hepatic insulin signaling, decreased expression of gluconeogenic genes and increased expression of glycogenic genes. Mechanistically, we show that insulin-stimulated phosphorylation of insulin receptor β (IRβ) is impaired in primary <i>Cyp2c44(-/-) </i>hepatocytes and this can be restored by cotreatment with EET-A and insulin. Plasma membrane fractionations of livers indicated that EET-A enhances the retention of IRβ in membrane rich fractions, thus potentiating its activation. Altogether, EET analogs ameliorate insulin signaling in a genetic model of hepatic insulin resistance by stabilizing membrane-associated IRβ and potentiating insulin signaling.

PO23-778 COMPARISON OF DIFFERENT METHODS TO STUDY POSTPRANDIAL LIPEMIA AND EFFECTS OF ROSUVASTATIN IN PATIENTS WITH INSULIN RESISTANCE AND PREMATURE CORONARY SCLEROSIS

2007 ◽  
Vol 8 (1) ◽  
pp. 207
Author(s):  
A.J.H.H. van Oostrom ◽  
A. Alipour ◽  
T.P. Sijmonsma ◽  
C. Verseyden ◽  
G.M. Dallinga-Thie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Postprandial Lipemia

scholarly journals TANK-binding kinase 1 mediates phosphorylation of insulin receptor at serine residue 994: a potential link between inflammation and insulin resistance

2009 ◽  
Vol 201 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Marina C Muñoz ◽  
Jorge F Giani ◽  
Marcos A Mayer ◽  
Jorge E Toblli ◽  
Daniel Turyn ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Genetic Model ◽  
Glycogen Synthase ◽  
Resistance Mechanism ◽  
Nuclear Factor Κb ◽  
Zucker Rats ◽  
Ang Ii ◽  
Iκb Kinase

The IκB kinase-β (IKK-β)/nuclear factor-κB signaling pathway has been suggested to link inflammation with obesity and insulin resistance. In addition, angiotensin (Ang) II is able to induce insulin resistance and an inflammatory state through Ang II receptor type 1 (AT1R). Accordingly, we examined whether inhibition of AT1R with irbesartan (IRB) can protect against the development of insulin resistance in obese Zucker rats (OZRs). IRB-treatment improved the insulin-stimulated insulin receptor (IR) phosphorylation at tyrosine (Tyr) residues 1158, 1162, 1163 (involved in activation of the IR kinase) and at Tyr972 (involved in substrate recognition). AT1R blockade also originated a dramatic increase in the phosphorylation of Akt and glycogen synthase kinase-3β. This was accompanied by a decrease in phosphorylation of IR on serine (Ser) 994, a residue that seems to be implicated in the regulation of IR kinase in OZR. In this study, we demonstrated that Ser994 of IR is a direct substrate for TANK-binding kinase 1 (TBK1), a new member of the IKK-related kinase family. TBK1 was found to co-immunoprecipitate with the IR, in the liver of OZR supporting an in vivo association between the IR and TBK1. Interestingly, a marked increase in the association between TBK1 and the IR was found in the liver of OZR as well as in other models of insulin resistance/diabetes. Taken together, these findings suggest that TBK1 could be involved in the insulin resistance mechanism related with IR Ser994 phosphorylation in a genetic model of diabetes.

We-P11:5 Postprandial lipemia and insulin resistance in individuals with and without type 2 diabetes

2006 ◽  
Vol 7 (3) ◽  
pp. 347 ◽  
Author(s):  
J. Rioja ◽  
F. Escalona ◽  
M.J. Ariza ◽  
M.T. Gonzalez-Alegre ◽  
E. Ulzurrun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Postprandial Lipemia

scholarly journals The subunit assembly state of the Mediator complex is nutrient-regulated and is dysregulated in a genetic model of insulin resistance and obesity

2019 ◽  
Vol 294 (23) ◽  
pp. 9076-9083 ◽  
Author(s):  
Dou Yeon Youn ◽  
Alus M. Xiaoli ◽  
Hyokjoon Kwon ◽  
Fajun Yang ◽  
Jeffrey E. Pessin
Keyword(s):  
Insulin Resistance ◽  
Genetic Model ◽  
Mediator Complex ◽  
Subunit Assembly

Puerarin Improves Vascular Insulin Resistance and Cardiovascular Remodeling in Salt-Sensitive Hypertension

2017 ◽  
Vol 45 (06) ◽  
pp. 1169-1184 ◽  
Author(s):  
Chunxiang Tan ◽  
Aimei Wang ◽  
Chan Liu ◽  
Yao Li ◽  
Yuepin Shi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiac Fibrosis ◽  
Metabolic Diseases ◽  
Genetic Model ◽  
Chinese Herb ◽  
Organ Damage ◽  
Jnk Pathway ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Salt Sensitive Hypertension

Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks. An additional group of DS rats was pretreated with puerarin and NS for 10 days, then switched to HS plus puerarin for five weeks. HS for five weeks increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and aortic hypertrophy with increased the expression of phosphor-ERK1/2 in the aorta and heart; puerarin attenuated cardiac and aortic hypertrophy, cardiac fibrosis and phosphor-ERK1/2 with a mild reduction in SBP. Hypertensive rats also manifested impairment of acetylcholine- and insulin-mediated vasorelaxation and insulin-mediated Akt and eNOS phosphorylation associated with the activation of NF[Formula: see text]B/TNF[Formula: see text]/JNK pathway. Puerarin improved acetylcholine- and insulin-mediated vasorelaxation and insulin-stimulated Akt/NO signaling with the inhibition of the NF[Formula: see text]B inflammatory pathway. Our results demonstrated that in salt-sensitive hypertension, puerarin improved vascular insulin action with cardiovascular beneficial effects. Our results found that the underlying mechanisms may involve its inhibition of NF[Formula: see text]B/JNK and ERK1/2 pathway. These results suggest that puerarin could be used as a new antihypertensive agent to expand our armamentarium for the prevention and treatment of end-organ damage in individuals with hypertension and metabolic diseases.

scholarly journals Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome

2008 ◽  
Vol 200 (3) ◽  
pp. 367-376 ◽  
Author(s):  
Alessandra Bitto ◽  
Domenica Altavilla ◽  
Antonio Bonaiuto ◽  
Francesca Polito ◽  
Letteria Minutoli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Postmenopausal Women ◽  
Experimental Model ◽  
Plasma Lipids ◽  
Genetic Model ◽  
Plasma Cholesterol ◽  
Vehicle Body ◽  
Genistein Treatment

Genistein aglycone, a soy derived isoflavone, has been demonstrated to be effective in reducing cardiovascular risk in postmenopausal women. We therefore investigated its effects in an experimental model of postmenopausal metabolic syndrome. Female spontaneously hypertensive obese rats (SHROB, n=40), a genetic model of syndrome X, and age-matched Wistar Kyoto (WKY, n=40) rats were used. A group of SHROB (n=20) and WKY (n=20) animals were ovariectomized (OVX). Four weeks after surgery all animals were randomized to receive either genistein (54 mg/human equivalent dose/day for 4 weeks), or vehicle. Body weight, food intake, systolic blood pressure (SBP), heart rate, plasma glucose, insulin resistance (HOMA-IR), total plasma cholesterol and triglycerides, and uterine weights were studied. Furthermore, we investigated acetylcholine- and sodium nitroprusside-induced relaxation of aortic rings as well as NG-L-arginine (L-NMA: 10–100 mM) induced vasoconstriction in phenylephrine-precontracted aortic segments. Liver expression of the peroxisome proliferator-activated receptor alpha (PPARA and gamma (PPARG was also assessed. OVX animals had a slight increase in SBP, body weight, insulin resistance, and plasma cholesterol. OVX-SHROB rats showed also impaired endothelial responses, blunted L-NMA induced contraction (L-NMA 100 mM, WKY=2.2±0.3 g/mg tissue; OVX-SHROB=1.1±0.4 g/mg tissue). Genistein treatment decreased SBP and plasma lipids, ameliorated endothelial dysfunction and insulin resistance, increased HDL cholesterol, and enhanced liver expression of PPARA and PPARG. Our data suggest that genistein is effective in ameliorating cardiovascular profiles in an experimental model of postmenopausal metabolic syndrome, attenuating the features of this disease. The effects of genistein are likely mediated by PPARA and PPARG receptors. This evidence would support the rationale for some pilot clinical trials using genistein in postmenopausal women affected by metabolic syndrome.

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