scholarly journals DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Mohamed Abu-Farha ◽  
Preethi Cherian ◽  
Irina Al-Khairi ◽  
Ali Tiss ◽  
Abdelkrim Khadir ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Insulin Signaling ◽  
Hsp 40

scholarly journals Overexpression of SH2-Containing Inositol Phosphatase 2 Results in Negative Regulation of Insulin-Induced Metabolic Actions in 3T3-L1 Adipocytes via Its 5′-Phosphatase Catalytic Activity

2001 ◽  
Vol 21 (5) ◽  
pp. 1633-1646 ◽  
Author(s):  
Tsutomu Wada ◽  
Toshiyasu Sasaoka ◽  
Makoto Funaki ◽  
Hiroyuki Hori ◽  
Shihou Murakami ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Phosphatase Activity ◽  
Insulin Signaling ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Dominant Negative ◽  
Inositol Phosphatase

ABSTRACT Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic actions of insulin including glucose uptake and glycogen synthesis. Although PI 3-kinase primarily functions as a lipid kinase which preferentially phosphorylates the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3-kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2) cDNA which possesses the 5′-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI 3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT-SHIP2) and 5′-phosphatase-defective SHIP2 (ΔIP-SHIP2) were overexpressed in 3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of insulin signaling including insulin-induced tyrosine phosphorylation of the insulin receptor β subunit and IRS-1, IRS-1 association with the p85 subunit, and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or ΔIP-SHIP2. Because WT-SHIP2 possesses the 5′-phosphatase catalytic region, its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression of ΔIP-SHIP2, indicating that ΔIP-SHIP2 functions in a dominant-negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known to possibly activate downstream targets Akt and protein kinase Cλ in vitro. Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt and protein kinase Cλ, whereas these activations were increased by expression of ΔIP-SHIP2 in vivo. Consistent with the regulation of downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and Glut4 translocation were decreased by expression of WT-SHIP2 and increased by expression of ΔIP-SHIP2. In addition, insulin-induced phosphorylation of GSK-3β and activation of PP1 followed by activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the expression of ΔIP-SHIP2. These results indicate that SHIP2 negatively regulates metabolic signaling of insulin via the 5′-phosphatase activity and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced activation of downstream molecules of PI 3-kinase leading to glucose uptake and glycogen synthesis.

scholarly journals In vitro contraction protects against palmitate-induced insulin resistance in C2C12 myotubes

2017 ◽  
Vol 313 (5) ◽  
pp. C575-C583 ◽  
Author(s):  
Stephan Nieuwoudt ◽  
Anny Mulya ◽  
Ciarán E. Fealy ◽  
Elizabeth Martelli ◽  
Srinivasan Dasarathy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Protective Role ◽  
Electrode System ◽  
C2c12 Myotubes ◽  
Noise Mapping ◽  
Whole Cell ◽  
Akt Phosphorylation

We are interested in understanding mechanisms that govern the protective role of exercise against lipid-induced insulin resistance, a key driver of type 2 diabetes. In this context, cell culture models provide a level of abstraction that aid in our understanding of cellular physiology. Here we describe the development of an in vitro myotube contraction system that provides this protective effect, and which we have harnessed to investigate lipid-induced insulin resistance. C2C12 myocytes were differentiated into contractile myotubes. A custom manufactured platinum electrode system and pulse stimulator, with polarity switching, provided an electrical pulse stimulus (EPS) (1 Hz, 6-ms pulse width, 1.5 V/mm, 16 h). Contractility was assessed by optical flow flied spot noise mapping and inhibited by application of ammonium acetate. Following EPS, myotubes were challenged with 0.5 mM palmitate for 4 h. Cells were then treated with or without insulin for glucose uptake (30 min), secondary insulin signaling activation (10 min), and phosphoinositide 3-kinase-α (PI3Kα) activity (5 min). Prolonged EPS increased non-insulin-stimulated glucose uptake (83%, P = 0.002), Akt (Thr308) phosphorylation ( P = 0.005), and insulin receptor substrate-1 (IRS-1)-associated PI3Kα activity ( P = 0.048). Palmitate reduced insulin-specific action on glucose uptake (−49%, P < 0.001) and inhibited insulin-stimulated Akt phosphorylation ( P = 0.049) and whole cell PI3Kα activity ( P = 0.009). The inhibitory effects of palmitate were completely absent with EPS pretreatment at the levels of glucose uptake, insulin responsiveness, Akt phosphorylation, and whole cell PI3Kα activity. This model suggests that muscle contraction alone is a sufficient stimulus to protect against lipid-induced insulin resistance as evidenced by changes in the proximal canonical insulin-signaling pathway.

1790-P: Akt2 Is Required for Glucose Uptake in Neuronal Insulin Signaling In Vitro

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1790-P
Author(s):  
MEDHA SHARMA ◽  
CHINMOY S. DEY
Keyword(s):  
Glucose Uptake ◽  
Insulin Signaling

Inhibition Of miR-16 In Vitro Decreases Glucose Uptake And Insulin Signaling

2019 ◽  
Vol 51 (Supplement) ◽  
pp. 974
Author(s):  
Seongkyun Lim ◽  
David E. Lee ◽  
Megan E. Rosa-Caldwell ◽  
Jacob L. Brown ◽  
Tyrone A. Washington ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Insulin Signaling

Green Tea Polyphenol Extract Regulates the Expression of Genes Involved in Glucose Uptake and Insulin Signaling in Rats Fed a High Fructose Diet

2007 ◽  
Vol 55 (15) ◽  
pp. 6372-6378 ◽  
Author(s):  
Heping Cao ◽  
Isabelle Hininger-Favier ◽  
Meghan A. Kelly ◽  
Rachida Benaraba ◽  
Harry D. Dawson ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Green Tea ◽  
Insulin Signaling ◽  
Tea Polyphenol ◽  
High Fructose Diet ◽  
Expression Of Genes ◽  
High Fructose ◽  
Green Tea Polyphenol

In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARγ in L6 myotubes

Phytomedicine ◽  
2006 ◽  
Vol 13 (6) ◽  
pp. 434-441 ◽  
Author(s):  
R. Anandharajan ◽  
S. Jaiganesh ◽  
N.P. Shankernarayanan ◽  
R.A. Viswakarma ◽  
A. Balakrishnan
Keyword(s):  
Glucose Uptake ◽  
Pi3 Kinase ◽  
Syzygium Cumini ◽  
Glut 4 ◽  
L6 Myotubes ◽  
Uptake Activity

scholarly journals Regulation of Mitochondria-Associated Membranes (MAMs) by NO/sGC/PKG Participates in the Control of Hepatic Insulin Response

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1319 ◽  
Author(s):  
Arthur Bassot ◽  
Marie-Agnès Chauvin ◽  
Nadia Bendridi ◽  
Jingwei Ji-Cao ◽  
Guillaume Vial ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Soluble Guanylate Cyclase ◽  
Insulin Response ◽  
Cyclophilin D ◽  
Hepatic Insulin Sensitivity ◽  
Physiological Conditions ◽  
Huh7 Cells ◽  
The Impact

Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) upregulates hepatic insulin sensitivity. Recently, contact sites between the endoplasmic reticulum and mitochondria named mitochondria-associated membranes (MAMs) emerged as a crucial hub for insulin signaling in the liver. As mitochondria are targets of NO, we explored whether NO regulates hepatic insulin sensitivity by targeting MAMs. In Huh7 cells, primary rat hepatocytes and mouse livers, enhancing NO concentration increased MAMs, whereas inhibiting eNOS decreased them. In vitro, those effects were prevented by inhibiting protein kinase G (PKG) and mimicked by activating soluble guanylate cyclase (sGC) and PKG. In agreement with the regulation of MAMs, increasing NO concentration improved insulin signaling, both in vitro and in vivo, while eNOS inhibition disrupted this response. Finally, inhibition of insulin signaling by wortmannin did not affect the impact of NO on MAMs, while experimental MAM disruption, using either targeted silencing of cyclophilin D or the overexpression of the organelle spacer fetal and adult testis-expressed 1 (FATE-1), significantly blunted the effects of NO on both MAMs and insulin response. Therefore, under physiological conditions, NO participates to the regulation of MAM integrity through the sGC/PKG pathway and concomitantly improves hepatic insulin sensitivity. Altogether, our data suggest that the induction of MAMs participate in the impact of NO on hepatocyte insulin response.

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