Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

Vasohibin-1 (Vash1), originally isolated as an endothelium-derived angiogenesis inhibitor, has a characteristic of promoting stress tolerance in endothelial cells (ECs). We therefore speculated that the lack of the vash1 gene would result in a short lifespan. However, to our surprise, vash1−/− mice lived significantly longer with a milder senescence phenotype than wild-type (WT) mice. We sought the cause of this healthy longevity and found that vash1−/− mice exhibited mild insulin resistance along with reduced expression of the insulin receptor (insr), insulin receptor substrate 1 (irs-1), and insulin receptor substrate 2 (irs-2) in their white adipose tissue (WAT) but not in their liver or skeletal muscle. The expression of vash1 dominated in the WAT among those 3 organs. Importantly, vash1−/− mice did not develop diabetes even when fed a high-fat diet. These results indicate that the expression of vash1 was required for the normal insulin sensitivity of the WAT and that the target molecules for this activity were insr, irs1, and irs2. The lack of vash1 caused mild insulin resistance without the outbreak of overt diabetes and might contribute to healthy longevity.

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Timosaponin B-II Ameliorates Palmitate-Induced Insulin Resistance and Inflammation via IRS-1/PI3K/Akt and IKK/NF-κB Pathways

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500415 ◽

2016 ◽

Vol 44 (04) ◽

pp. 755-769 ◽

Cited By ~ 17

Author(s):

Yong-Liang Yuan ◽

Bao-Qin Lin ◽

Chun-Feng Zhang ◽

Ling-Ling Cui ◽

Shi-Xia Ruan ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Receptor ◽

Hepg2 Cells ◽

Serine Phosphorylation ◽

Insulin Receptor Substrate ◽

Phosphatidylinositol 3 Kinase ◽

Insulin Receptor Substrate 1 ◽

Akt Activation ◽

Related Proteins ◽

Anemarrhena Asphodeloides

This study aimed to investigate the effect of timosaponin B-II (TB-II) on palmitate (PA)-induced insulin resistance and inflammation in HepG2 cells, and probe the potential mechanisms. TB-II, a main ingredient of the traditional Chinese medicine Anemarrhena asphodeloides Bunge, notably ameliorated PA-induced insulin resistance and inflammation, and significantly improved cell viability, decreased PA-induced production of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]) and interleukin-6 (IL-6) levels. Further, TB-II treatment notably decreased malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, and improved superoxide dismutase (SOD) and nitric oxide (NO). TB-II also reduced HepG2 cells apoptosis. Insulin receptor substrate-1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/Akt and inhibitor of nuclear factor [Formula: see text]-B kinase (IKK)/NF-[Formula: see text]B pathways-related proteins, and IKK[Formula: see text], p65 phosphorylation, serine phosphorylation of insulin receptor substrate-1 (IRS-1) at S307, tyrosine phosphorylation of IRS-1, and Akt activation were determined by Western blot. Compared to model group, TB-II significantly downregulated the expression of p-NF-[Formula: see text]Bp65, p-IKK[Formula: see text], p-IRS-1, p-PI3K and p-Akt. TB-II is a promising potential agent for the management of palmitate-induced insulin resistance and inflammation, which might be via IR/IRS-1/PI3K/Akt and IKK/NF-[Formula: see text]B pathways.

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Rescuing 3T3-L1 Adipocytes from Insulin Resistance Induced by Stimulation of Akt-Mammalian Target of Rapamycin/p70 S6 Kinase (S6K1) Pathway and Serine Phosphorylation of Insulin Receptor Substrate-1: Effect of Reduced Expression of p85α Subunit of Phosphatidylinositol 3-Kinase and S6K1 Kinase

Endocrinology ◽

10.1210/en.2008-0437 ◽

2008 ◽

Vol 150 (3) ◽

pp. 1165-1173 ◽

Cited By ~ 12

Author(s):

Rebecca Adochio ◽

J. Wayne Leitner ◽

Reed Hedlund ◽

Boris Draznin

Keyword(s):

Insulin Resistance ◽

Insulin Receptor ◽

Mammalian Target Of Rapamycin ◽

Serine Phosphorylation ◽

Insulin Receptor Substrate ◽

Phosphatidylinositol 3 Kinase ◽

Insulin Receptor Substrate 1 ◽

S6 Kinase ◽

P70 S6 Kinase ◽

Stimulation Of

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Inhibition of Thrombin Action Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice

Endocrinology ◽

10.1210/en.2009-0661 ◽

2010 ◽

Vol 151 (2) ◽

pp. 513-519 ◽

Cited By ~ 21

Author(s):

Masatomo Mihara ◽

Ken-ichi Aihara ◽

Yasumasa Ikeda ◽

Sumiko Yoshida ◽

Mizuho Kinouchi ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Receptor ◽

Coagulation Factor ◽

Macrophage Infiltration ◽

Factor Vii ◽

Thrombin Inhibitor ◽

Insulin Receptor Substrate ◽

Insulin Receptor Substrate 1 ◽

Inhibition Of Thrombin

The binding of thrombin to its receptor stimulates inflammatory cytokines including IL-6 and monocyte chemoattractant protein-1 (MCP-1); both are associated with the development of insulin resistance. Because increased adiposity enhanced the expression of coagulation factor VII that stimulates the coagulation pathway in adipose tissue, we tested whether the inhibition of thrombin action ameliorates insulin resistance in obese diabetic (Lpr−/−:db/db) mice. The 4-wk administration of argatroban, a selective thrombin inhibitor, reduced fasting plasma glucose and ameliorated insulin resistance in these mice. It also reduced adipocyte size and macrophage infiltration into adipose tissue. The aberrant gene expression of MCP-1, IL-6, adiponectin, and factor VII and suppressed insulin receptor substrate-1-Akt signaling in adipose tissue of db/db mice were reversed by argatroban treatment. These results demonstrate that increased adiposity enhances the production of thrombin in adipose tissue by stimulating factor VII expression and suggest that increased thrombin activity in adipose tissue plays an important role in the development of insulin resistance via enhancing MCP-1 production, leading to macrophage infiltration and insulin receptor substrate-1-Akt pathway inactivation.

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