Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease

2015 ◽  
Vol 156 ◽  
pp. 64-74 ◽  
Author(s):  
G.J. Hein ◽  
C.G. Panzani ◽  
F.M. Rodríguez ◽  
N.R. Salvetti ◽  
P.U. Díaz ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Insulin Signaling ◽  
Ovarian Follicles ◽  
Insulin Signaling Pathway ◽  
Ovarian Disease ◽  
Impaired Insulin ◽  
Cystic Ovarian Disease

Impaired insulin signaling pathway in skeletal muscle from subjects with insulinoma

2000 ◽  
Vol 50 ◽  
pp. 159
Author(s):  
Andrej Janez ◽  
Franc Mrevlje ◽  
Prem M Sharma ◽  
Andreja Kocijancic
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Signaling Pathway ◽  
Impaired Insulin

Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation

2021 ◽  
Author(s):  
Saori Kakehi ◽  
Yoshifumi Tamura ◽  
Shin-ichi Ikeda ◽  
Naoko Kaga ◽  
Hikari Taka ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Physical Inactivity ◽  
Insulin Signaling Pathway ◽  
Dominant Negative ◽  
Short Term ◽  
Intramyocellular Lipids ◽  
Cast Immobilization ◽  
Impaired Insulin

Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. To model physical inactivity, we applied 24-h hind-limb cast immobilization (HCI) to mice with normal or high fat diet (HFD), and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. While 2-wk HFD alone did not alter intramyocellular diacylglycerol (IMDG) accumulation, HCI alone increased it by 1.9-fold and HCI after HFD further increased it by 3.3-fold. Parallel to this, we found increased PKCε activity, reduced insulin-induced 2-deoxy-glucose (2-DOG) uptake, and reduced phosphorylation of IRβ and Akt, key molecules for insulin signaling pathway. Lipin1, which converts phosphatidic acid to diacylglycerol, showed increase of its activity by HCI, and dominant-negative lipin1 expression in muscle prevented HCI-induced IMDG accumulation and impaired insulin-induced 2-DOG uptake. Further, 24-h leg cast immobilization in human increased lipin1 expression. Thus, even short-term immobilization increases IMDG and impairs insulin sensitivity in muscle via enhanced lipin1 activity.

scholarly journals Hypochlorous acid via peroxynitrite activates protein kinase Cθ and insulin resistance in adipocytes

2014 ◽  
Vol 54 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Jun Zhou ◽  
Qilong Wang ◽  
Ye Ding ◽  
Ming-Hui Zou
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Hypochlorous Acid ◽  
Insulin Signaling Pathway ◽  
Serine Phosphorylation ◽  
Impaired Insulin ◽  
Genetic Deletion

We recently reported that genetic deletion of myeloperoxidase (MPO) alleviates obesity-related insulin resistance in mice in vivo. How MPO impairs insulin sensitivity in adipocytes is poorly characterized. As hypochlorous acid (HOCl) is a principal oxidant product generated by MPO, we evaluated the effects of HOCl on insulin signaling in adipocytes differentiated from 3T3-L1 cells. Exposure of 3T3-L1 adipocytes to exogenous HOCl (200 μmol/l) attenuated insulin-stimulated 2-deoxyglucose uptake, GLUT4 translocation, and insulin signals, including tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and phosphorylation of Akt. Furthermore, treatment with HOCl induced phosphorylation of IRS1 at serine 307, inhibitor κB kinase (IKK), c-Jun NH2-terminal kinase (JNK), and phosphorylation of PKCθ (PKCθ). In addition, genetic and pharmacological inhibition of IKK and JNK abolished serine phosphorylation of IRS1 and impairment of insulin signaling by HOCl. Furthermore, knockdown of PKCθ using siRNA transfection suppressed phosphorylation of IKK and JNK and consequently attenuated the HOCl-impaired insulin signaling pathway. Moreover, activation of PKCθ by peroxynitrite was accompanied by increased phosphorylation of IKK, JNK, and IRS1-serine 307. In contrast, ONOO− inhibitors abolished HOCl-induced phosphorylation of PKCθ, IKK, JNK, and IRS1-serine 307, as well as insulin resistance. Finally, high-fat diet (HFD)-induced insulin resistance was associated with enhanced phosphorylation of PKCθ, IKK, JNK, and IRS1 at serine 307 in white adipose tissues from WT mice, all of which were not found in Mpo knockout mice fed HFDs. We conclude that HOCl impairs insulin signaling pathway by increasing ONOO− mediated phosphorylation of PKCθ, resulting in phosphorylation of IKK/JNK and consequent serine phosphorylation of IRS1 in adipocytes.

scholarly journals Increased β-Cell Apoptosis and Impaired Insulin Signaling Pathway Contributes to the Onset of Diabetes in OLETF Rats

2008 ◽  
Vol 21 (5-6) ◽  
pp. 445-454 ◽  
Author(s):  
Jiawei Zhao ◽  
Nina Zhang ◽  
Min He ◽  
Zhihong Yang ◽  
Wei Tong ◽  
...  
Keyword(s):  
Beta Cell ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Cell Apoptosis ◽  
Insulin Signaling Pathway ◽  
Beta Cell Apoptosis ◽  
Oletf Rats ◽  
Impaired Insulin ◽  
Onset Of Diabetes

scholarly journals MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle

2020 ◽  
Author(s):  
Clothilde Philouze ◽  
Sophie Turban ◽  
Béatrice Cremers ◽  
Audrey Caliez ◽  
Gwladys Lamarche ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Response ◽  
Muscle Cells ◽  
Insulin Signaling Pathway ◽  
Akt Phosphorylation ◽  
Impaired Insulin

AbstractIn type 2 diabetes (T2D), both muscle and liver are severely resistant to insulin action. Muscle insulin resistance accounts for more than 80% of the impairment in total body glucose disposal in T2D patients and is often characterized by an impaired insulin signaling. Mitsugumin 53 (MG53), a muscle-specific TRIM family protein initially identified as a key regulator of cell membrane repair machinery has been suggested to be a critical regulator of muscle insulin signaling pathway by acting as ubiquitin E3 ligase targeting both the insulin receptor and insulin receptor substrate 1 (IRS1). Here, we show using in vitro and in vivo approaches that MG53 is not a critical regulator of insulin signaling and glucose homeostasis. First, MG53 expression is not consistently regulated in skeletal muscle from various preclinical models of insulin resistance. Second, MG53 gene knock-down in muscle cells does not lead to impaired insulin response as measured by Akt phosphorylation on Serine 473 and glucose uptake. Third, recombinant human MG53 does not alter insulin response in both differentiated C2C12 and human skeletal muscle cells. Fourth, ectopic expression of MG53 in HEK293 cells lacking endogenous MG53 expression fails to alter insulin response as measured by Akt phosphorylation. Finally, both male and female mg53 −/− mice were not resistant to high fat induced obesity and glucose intolerance compared to wild-type mice. Taken together, these results strongly suggest that MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle.

scholarly journals MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245179
Author(s):  
Clothilde Philouze ◽  
Sophie Turban ◽  
Beatrice Cremers ◽  
Audrey Caliez ◽  
Gwladys Lamarche ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Response ◽  
Muscle Cells ◽  
Insulin Signaling Pathway ◽  
Akt Phosphorylation ◽  
Impaired Insulin

In type 2 diabetes (T2D), both muscle and liver are severely resistant to insulin action. Muscle insulin resistance accounts for more than 80% of the impairment in total body glucose disposal in T2D patients and is often characterized by an impaired insulin signaling. Mitsugumin 53 (MG53), a muscle-specific TRIM family protein initially identified as a key regulator of cell membrane repair machinery has been suggested to be a critical regulator of muscle insulin signaling pathway by acting as ubiquitin E3 ligase targeting both the insulin receptor and insulin receptor substrate 1 (IRS1). Here, we show using in vitro and in vivo approaches that MG53 is not a critical regulator of insulin signaling and glucose homeostasis. First, MG53 expression is not consistently regulated in skeletal muscle from various preclinical models of insulin resistance. Second, MG53 gene knock-down in muscle cells does not lead to impaired insulin response as measured by Akt phosphorylation on Serine 473 and glucose uptake. Third, recombinant human MG53 does not alter insulin response in both differentiated C2C12 and human skeletal muscle cells. Fourth, ectopic expression of MG53 in HEK293 cells lacking endogenous MG53 expression fails to alter insulin response as measured by Akt phosphorylation. Finally, both male and female mg53 -/- mice were not resistant to high fat induced obesity and glucose intolerance compared to wild-type mice. Taken together, these results strongly suggest that MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle.

scholarly journals Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2268
Author(s):  
Dina Medina-Vera ◽  
Juan Antonio Navarro ◽  
Rubén Tovar ◽  
Cristina Rosell-Valle ◽  
Alfonso Gutiérrez-Adan ◽  
...  
Keyword(s):  
Oral Administration ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Response ◽  
Pharmacological Action ◽  
Akt Signaling ◽  
Insulin Signaling Pathway ◽  
Acute Administration ◽  
Insulin Sensitizer ◽  
Peripheral Tissues

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.

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