Amino acid modified gadofullerene protects against insulin resistance induced by oxidative stress in 3T3-L1 adipocytes

2020 ◽  
Vol 8 (33) ◽  
pp. 7521-7527
Author(s):  
Tong Yu ◽  
Wang Jia ◽  
Mingming Zhen ◽  
Yue Zhou ◽  
Jie Li ◽  
...  

GF-Ala afforded a significant protection against insulin resistance induced by oxidative stress in 3T3-L1 adipocytes. It could reverse the increase of JNK activation and decreases of insulin-stimulated PI3K, Akt, p70S6K activation and GLUT4 translocation.

2013 ◽  
Vol 5 (2) ◽  
pp. 101 ◽  
Author(s):  
Ritawaty Ritawaty ◽  
Indriyanti Rafi Sukmawati ◽  
Ilhamjaya Patellongi ◽  
Ferry Sandra

BACKGROUND: Gamma glutamyltransferase (GGT) was reported recently to be associated with inflammation, oxidative stress and increased amino acid. However, role of GGT in insulin resistance pathomechanism is not exactly known. Therefore correlation of GGT with inflammation, oxidative stress and elevated amino acid, in men with central obesity need to be confirmed.METHODS: A cross-sectional study was designed. Men with central obesity were recruited and selected. Anthropometric parameters, creatinine, hs-CRP, fasting glucose, fasting insulin, glutathione peroxidase (GPx) activity, GGT, plasma total cysteine (tCys) and fatty liver were measured. Subjects were then divided in 4 groups based on waist circumference (WC) and fatty liver: Group I: WC ≤100 cm, without fatty liver; Group II: WC ≤100 cm, with fatty liver; Group III: WC >100 cm, without fatty liver; Group IV: WC >100 cm, with fatty liver. All biochemical characteristics in each group were then statistically analyzed.RESULTS: Seventy-two men with central obesity were selected. Numbers of subjects in each group were: Group I: n=33; Group II: n=5; Group III: n=17; Group IV: n=17. We found significant difference of HOMA-IR between Group I and IV, significant correlation between GGT and HOMAIR, and significant negative correlation between tCys with HOMA-IR in Group IV.CONCLUSION: GGT was significantly correlated with HOMA-IR in men with WC >100 cm and fatty liver. Further investigation with more subjects is necessary to determine clear GGT cut-off to distinguish subjects with fatty liver and insulin resistance.KEYWORDS: GGT, hs-CRP, GPx, tCys, HOMA-IR, insulin resistance


Diabetes ◽  
2017 ◽  
Vol 66 (12) ◽  
pp. 2973-2986 ◽  
Author(s):  
Sara A. Litwak ◽  
Lokman Pang ◽  
Sandra Galic ◽  
Mariana Igoillo-Esteve ◽  
William J. Stanley ◽  
...  

2021 ◽  
Author(s):  
Ada Admin ◽  
Regine Å. Jersin ◽  
Divya Sri Priyanka Tallapragada ◽  
André Madsen ◽  
Linn Skartveit ◽  
...  

Elucidation of mechanisms that govern lipid storage, oxidative stress and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter 1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish <i>in vivo</i> accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA-sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of <i>SCD</i> (lipid storage) and downregulation of <i>CPT1A</i> (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance and type 2 diabetes.


2021 ◽  
Author(s):  
Ada Admin ◽  
Regine Å. Jersin ◽  
Divya Sri Priyanka Tallapragada ◽  
André Madsen ◽  
Linn Skartveit ◽  
...  

Elucidation of mechanisms that govern lipid storage, oxidative stress and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter 1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish <i>in vivo</i> accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA-sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of <i>SCD</i> (lipid storage) and downregulation of <i>CPT1A</i> (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance and type 2 diabetes.


2011 ◽  
Vol 110 (2) ◽  
pp. 451-457 ◽  
Author(s):  
Anisha A. Gupte ◽  
Gregory L. Bomhoff ◽  
Chad D. Touchberry ◽  
Paige C. Geiger

Aging is associated with insulin resistance and decreased insulin-stimulated glucose uptake into skeletal muscle. Although the mechanisms underlying age-related insulin resistance are not clearly defined, impaired defense against inflammation and tissue oxidative stress are likely causes. Heat shock proteins (HSPs) have been shown to protect tissue from oxidative stress and inhibit the activation of stress kinases such as JNK, known to interfere with the insulin signaling pathway. While the induction of HSPs via chronic heat treatment has been shown to protect skeletal muscle from obesity-related insulin resistance, the ability of heat treatment to improve insulin action in aged skeletal muscle is not known. In the present study, one bout of in vivo heat treatment applied to 24-mo-old Fischer 344 rats improved insulin-stimulated glucose uptake after 24 h in slow-twitch soleus muscles. In vitro heat treatment applied to young (3-mo-old) and aged (24-mo-old) soleus muscles increased expression of HSP72 and inhibited anisomycin-induced activation of JNK. In contrast, heat treatment had no effect on p38 MAPK, a MAPK strongly activated with anisomycin. Prior inhibition of HSP72 transcription with the pharmacological inhibitor KNK437 eliminated the ability of heat treatment to blunt JNK activation. This suggests that the ability of heat treatment to inhibit JNK activation in skeletal muscle is dependent on increased HSP72 expression. In conclusion, an acute bout of heat treatment can increase insulin-stimulated glucose uptake in aged skeletal muscle, with the underlying mechanism likely to be HSP72-mediated JNK inhibition.


Author(s):  
Reveka Gyftaki ◽  
Sofia Gougoura ◽  
Nikolaos Kalogeris ◽  
Vasiliki Loi ◽  
George Koukoulis ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document