scholarly journals DhHP-6 ameliorates hepatic oxidative stress and insulin resistance in type 2 diabetes mellitus through the PI3K/AKT and AMPK pathway

2020 ◽  
Vol 477 (12) ◽  
pp. 2363-2381
Author(s):  
Kai Wang ◽  
Yuting Liang ◽  
Yu Su ◽  
Liping Wang
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Akt Phosphorylation ◽  
Ampk Pathway ◽  
Ampk Phosphorylation ◽  
Improve Insulin Resistance

Insulin resistance is one major features of type 2 diabetes mellitus (T2DM). Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6), a novel microperoxidase mimetic designed and synthesized based on microperoxidase 11 (MP-11), can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we showed that oral DhHP-6 could reduce blood glucose and improve insulin resistance. To investigate the mechanisms of how DhHP-6 ameliorates oxidative stress and insulin resistance, we established T2DM mouse models and glucosamine-induced HepG2 cell insulin resistance models. The results suggested that DhHP-6 decreased blood glucose, increased antioxidant enzyme activity, and inhibited glycogen synthesis in T2DM mice. In addition, DhHP-6 improved insulin resistance by activating phosphatidylinositol 3-kinase (PI3K)/AKT, and AMP-activated protein kinase (AMPK) pathway in T2DM mice. Furthermore, DhHP-6 also activated PI3K/AKT and AMPK pathway in glucosamine-induced HepG2 cells. However, LY294002 did not completely inhibit AKT phosphorylation, and partially inhibited AMPK phosphorylation, whilst compound C only partially reduced AMPK phosphorylation, and also partially inhibited AKT phosphorylation, suggesting that AKT and AMPK interact to improve insulin resistance. Thus, these data suggest that DhHP-6 attenuates insulin resistance via the PI3K/AKT and AMPK pathway.

scholarly journals Designing a late-stage type 2 diabetes mellitus model with brain insulin resistance and oxidative stress

2021 ◽  
Author(s):  
Rocío Redondo-Castillejo ◽  
Marina Hernández-Martín ◽  
Luis García-García ◽  
Juana Benedí ◽  
Adrián Macho-González ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Late Stage ◽  
Brain Insulin ◽  
Brain Insulin Resistance ◽  
And Oxidative Stress

Oatmeal Diet Days May Improve Insulin Resistance in Patients with Type 2 Diabetes Mellitus

2013 ◽  
Vol 20 (6) ◽  
pp. 465-468 ◽  
Author(s):  
Roland Zerm ◽  
Bert Helbrecht ◽  
Michael Jecht ◽  
Angelika Hein ◽  
Elke Millet ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Improve Insulin Resistance

scholarly journals The PPARβ/δ-AMPK Connection in the Treatment of Insulin Resistance

2021 ◽  
Vol 22 (16) ◽  
pp. 8555
Author(s):  
David Aguilar-Recarte ◽  
Xavier Palomer ◽  
Walter Wahli ◽  
Manuel Vázquez-Carrera
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
New Drugs ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Ampk Pathway ◽  
Antidiabetic Effects

The current treatment options for type 2 diabetes mellitus do not adequately control the disease in many patients. Consequently, there is a need for new drugs to prevent and treat type 2 diabetes mellitus. Among the new potential pharmacological strategies, activators of peroxisome proliferator-activated receptor (PPAR)β/δ show promise. Remarkably, most of the antidiabetic effects of PPARβ/δ agonists involve AMP-activated protein kinase (AMPK) activation. This review summarizes the recent mechanistic insights into the antidiabetic effects of the PPARβ/δ-AMPK pathway, including the upregulation of glucose uptake, muscle remodeling, enhanced fatty acid oxidation, and autophagy, as well as the inhibition of endoplasmic reticulum stress and inflammation. A better understanding of the mechanisms underlying the effects resulting from the PPARβ/δ-AMPK pathway may provide the basis for the development of new therapies in the prevention and treatment of insulin resistance and type 2 diabetes mellitus.

scholarly journals Glutathione Peroxidase 3 Mediates the Antioxidant Effect of Peroxisome Proliferator-Activated Receptor γ in Human Skeletal Muscle Cells

2008 ◽  
Vol 29 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Sung Soo Chung ◽  
Min Kim ◽  
Byoung-Soo Youn ◽  
Nam Seok Lee ◽  
Ji Woo Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells

ABSTRACT Oxidative stress plays an important role in the pathogenesis of insulin resistance and type 2 diabetes mellitus and in diabetic vascular complications. Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor γ (PPARγ) agonists, improve insulin sensitivity and are currently used for the treatment of type 2 diabetes mellitus. Here, we show that TZD prevents oxidative stress-induced insulin resistance in human skeletal muscle cells, as indicated by the increase in insulin-stimulated glucose uptake and insulin signaling. Importantly, TZD-mediated activation of PPARγ induces gene expression of glutathione peroxidase 3 (GPx3), which reduces extracellular H2O2 levels causing insulin resistance in skeletal muscle cells. Inhibition of GPx3 expression prevents the antioxidant effects of TZDs on insulin action in oxidative stress-induced insulin-resistant cells, suggesting that GPx3 is required for the regulation of PPARγ-mediated antioxidant effects. Furthermore, reduced plasma GPx3 levels were found in patients with type 2 diabetes mellitus and in db/db/DIO mice. Collectively, these results suggest that the antioxidant effect of PPARγ is exclusively mediated by GPx3 and further imply that GPx3 may be a therapeutic target for insulin resistance and diabetes mellitus.

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