scholarly journals Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats

2002 ◽  
Vol 92 (2) ◽  
pp. 736-744 ◽  
Author(s):  
Christine Y. Christ ◽  
Desmond Hunt ◽  
Joe Hancock ◽  
Rebeca Garcia-Macedo ◽  
Lawrence J. Mandarino ◽  
...  
Keyword(s):  
Exercise Training ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Exercise Bout ◽  
Pi3 Kinase ◽  
Serine Phosphorylation ◽  
Zucker Rats ◽  
Receptor Signaling ◽  
Insulin Receptor Signaling ◽  
Obese Zucker Rats

Exercise training improves skeletal muscle insulin sensitivity in the obese Zucker rat. The purpose of this study was to investigate whether the improvement in insulin action in response to exercise training is associated with enhanced insulin receptor signaling. Obese Zucker rats were trained for 7 wk and studied by using the hindlimb-perfusion technique 24 h, 96 h, or 7 days after their last exercise training bout. Insulin-stimulated glucose uptake (traced with 2-deoxyglucose) was significantly reduced in untrained obese Zucker rats compared with lean controls (2.2 ± 0.17 vs. 5.4 ± 0.46 μmol · g−1 · h−1). Glucose uptake was normalized 24 h after the last exercise bout (4.9 ± 0.41 μmol · g−1 · h−1) and remained significantly elevated above the untrained obese Zucker rats for 7 days. However, exercise training did not increase insulin receptor or insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3-kinase) activity associated with IRS-1 or tyrosine phosphorylated immunoprecipitates, or Akt serine phosphorylation. These results are consistent with the hypothesis that, in obese Zucker rats, adaptations occur during training that lead to improved insulin-stimulated muscle glucose uptake without affecting insulin receptor signaling through the PI3-kinase pathway.

Muscle glucose uptake of obese Zucker rats trained at two different intensities

1991 ◽  
Vol 70 (1) ◽  
pp. 36-42 ◽  
Author(s):  
M. E. Willems ◽  
J. T. Brozinick ◽  
C. E. Torgan ◽  
M. Y. Cortez ◽  
J. L. Ivy
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Exercise Bout ◽  
Zucker Rats ◽  
Muscle Insulin Resistance ◽  
Obese Zucker Rat ◽  
Training Response ◽  
Obese Zucker Rats ◽  
The Difference

Exercise training reduces the muscle insulin resistance of the obese Zucker rat. The purpose of the present study was to determine whether the magnitude of this training response is exercise intensity specific. Obese Zucker rats were randomly divided into sedentary (SED), low-intensity (LI), and high-intensity (HI) exercise groups. For the LI rats, exercise training consisted of running on a rodent treadmill at 18 m/min up an 8% grade for 90 min. Rats in the HI group ran at 24 m/min up an 8% grade for four 17-min bouts with 3 min between bouts. Both exercise groups performed the same amount of work and trained 5 days/wk for 7 wk. To evaluate muscle insulin resistance, rat hindlimbs were perfused for 30 min with perfusate containing 6 mM glucose (0.15 mu Ci of D-[14C(U)] glucose/ml) and either a maximal (10.0 mU/ml) or a submaximal (0.50 mU/ml) insulin concentration. Perfusions were performed 48–56 h after the last exercise bout and a 12-h fast. In the presence of 0.5 mU/ml insulin, the rate of muscle glucose uptake was found to be significantly faster for the HI (9.56 +/- 0.66 mumol.h-1.g-1) than for the LI (7.72 +/- 0.65 mumol.h-1.g-1) and SED (6.64 +/- 0.44 mumol.h-1.g-1) rats. The difference in glucose uptake between the LI and SED rats was not significant. In the presence of 10.0 mU/ml insulin, the rate of glucose uptake was significantly faster for the HI (16.43 +/- 1.02 mumol.h-1.g-1) than for the LI rats (13.76 +/- 0.84 mumol.h-1.g-1) and significantly faster for the LI than for the SED rats (11.02 +/- 0.35 mumol.h-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling

BMC Cancer ◽  
2007 ◽  
Vol 7 (1) ◽  
Author(s):  
Kiyosumi Shibata ◽  
Hiroaki Kajiyama ◽  
Kazuhiko Ino ◽  
Akihiro Nawa ◽  
Seiji Nomura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Insulin Receptor ◽  
Endometrial Carcinoma ◽  
Glucose Uptake ◽  
Carcinoma Cells ◽  
Receptor Signaling ◽  
Insulin Receptor Signaling

scholarly journals PDGF-induced vascular smooth muscle cell proliferation is associated with dysregulation of insulin receptor substrates

2011 ◽  
Vol 300 (6) ◽  
pp. C1375-C1385 ◽  
Author(s):  
Yan Zhao ◽  
Swarajit K. Biswas ◽  
Patrick H. McNulty ◽  
Mark Kozak ◽  
John Y. Jun ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Insulin Receptor ◽  
Serine Phosphorylation ◽  
Phenotypic Switching ◽  
Dependent Manner ◽  
Receptor Signaling ◽  
Vsmc Proliferation ◽  
Insulin Receptor Substrates ◽  
Insulin Receptor Signaling

In vascular smooth muscle cells (VSMCs), platelet-derived growth factor (PDGF) plays a major role in inducing phenotypic switching from contractile to proliferative state. Importantly, VSMC phenotypic switching is also determined by the phosphorylation state/expression levels of insulin receptor substrate (IRS), an intermediary signaling component that is shared by insulin and IGF-I. To date, the roles of PDGF-induced key proliferative signaling components including Akt, p70S6kinase, and ERK1/2 on the serine phosphorylation/expression of IRS-1 and IRS-2 isoforms remain unclear in VSMCs. We hypothesize that PDGF-induced VSMC proliferation is associated with dysregulation of insulin receptor substrates. Using human aortic VSMCs, we demonstrate that prolonged PDGF treatment led to sustained increases in the phosphorylation of protein kinases such as Akt, p70S6kinase, and ERK1/2, which mediate VSMC proliferation. In addition, PDGF enhanced IRS-1/IRS-2 serine phosphorylation and downregulated IRS-2 expression in a time- and concentration-dependent manner. Notably, phosphoinositide 3-kinase (PI 3-kinase) inhibitor (PI-103) and mammalian target of rapamycin inhibitor (rapamycin), which abolished PDGF-induced Akt and p70S6kinase phosphorylation, respectively, blocked PDGF-induced IRS-1 serine phosphorylation and IRS-2 downregulation. In contrast, MEK1/ERK inhibitor (U0126) failed to block PDGF-induced IRS-1 serine phosphorylation and IRS-2 downregulation. PDGF-induced IRS-2 downregulation was prevented by lactacystin, an inhibitor of proteasomal degradation. Functionally, PDGF-mediated IRS-1/IRS-2 dysregulation resulted in the attenuation of insulin-induced IRS-1/IRS-2-associated PI 3-kinase activity. Pharmacological inhibition of PDGF receptor tyrosine kinase with imatinib prevented IRS-1/IRS-2 dysregulation and restored insulin receptor signaling. In conclusion, strategies to inhibit PDGF receptors would not only inhibit neointimal growth but may provide new therapeutic options to prevent dysregulated insulin receptor signaling in VSMCs in nondiabetic and diabetic states.

Abstract 657: PDGF versus Fructose Dysregulation of Insulin Receptor Signaling in Vascular Smooth Muscle Cells: Pioglitazone-mediated Sensitization of Insulin Receptor Signaling is Associated with Diminished Vascular Smooth Muscle Cell Proliferation

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Islam Osman ◽  
Lakshman Segar
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Insulin Receptor ◽  
Vascular Smooth Muscle Cells ◽  
Insulin Signaling ◽  
Serine Phosphorylation ◽  
Receptor Signaling ◽  
Vsmc Proliferation ◽  
Insulin Receptor Signaling

Previous studies have shown that PDGF-induced activation of mTOR/p70S6kinase signaling is associated with dysregulation of insulin receptor substrates (IRS1 and IRS2) in vascular smooth muscle cells (VSMCs). In addition, pioglitazone (PIO, an antidiabetic drug) has been shown to inhibit mTOR/p70S6kinase signaling thereby suppressing PDGF-induced VSMC proliferation. The role of IRS1/IRS2 on proliferative signaling events has not yet been examined in VSMCs treated with fructose (an agent that induces insulin resistance) or PIO (an insulin sensitizer). In the present study, unlike PDGF treatment (48 hr) that enhanced IRS serine phosphorylation and diminished IRS2 expression, exposure of human aortic VSMCs to D-fructose (5.5 to 25 mM) for 48 hr resulted in a concentration-dependent increase in IRS1 serine phosphorylation (up to ~5-fold , n = 3), but without any changes in IRS2 protein expression. In D-fructose-treated VSMCs, Akt phosphorylation in response to acute insulin exposure (6 min) was markedly decreased (~69%, n = 3), suggesting that IRS1 serine phosphorylation alone is sufficient to dysregulate insulin receptor signaling. In addition, D-fructose treatment led to a further increase in PDGF-induced VSMC proliferation (~40%, n = 3). Furthermore, we examined the effects of PIO on PDGF-induced dysregulation of IRS in VSMCs. Notably, PIO treatment (30 μM, 48 hr) by itself led to an upregulation of IRS-2 expression (~2.5-fold) and also diminished PDGF-induced IRS1 serine phosphorylation (~63%). Under these conditions, PIO treatment resulted in significant inhibition of PDGF-induced cyclin D1 expression, Rb phosphorylation, and VSMC proliferation (~83%, n = 3). In conclusion, the present study reveals that dysregulated insulin signaling (by PDGF and fructose) is associated with enhanced VSMC proliferation, whereas insulin sensitization (by PIO) is associated with inhibition of VSMC proliferation. Together, these findings underscore the significance of intact insulin signaling toward limiting exaggerated VSMC proliferation in the vessel wall.

Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats

1993 ◽  
Vol 265 (3) ◽  
pp. E419-E427 ◽  
Author(s):  
J. T. Brozinick ◽  
G. J. Etgen ◽  
B. B. Yaspelkis ◽  
H. Y. Kang ◽  
J. L. Ivy
Keyword(s):  
Plasma Membrane ◽  
Exercise Training ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Protein Concentration ◽  
Citrate Synthase ◽  
Zucker Rats ◽  
Glut 4 ◽  
Basal Plasma ◽  
Obese Zucker Rats

The rates of muscle glucose uptake of trained (TR) and untrained (UT) obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin) in the presence of a maximally stimulating concentration of insulin (10 mU/ml) and after muscle contraction elicited by electrical stimulation of the sciatic nerve. Perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H]glucose. Muscle GLUT-4 concentration was determined by Western blot analysis and expressed as a percentage of a heart standard. The rates of insulin-stimulated glucose uptake were significantly higher in the plantaris, red gastrocnemius (RG), and white gastrocnemius (WG), but not the soleus or extensor digatorum longus (EDL) of TR compared with UT rats. After muscle contraction the rates of glucose uptake in the TR rats were significantly higher in the soleus, plantaris, and RG. TR rats had significantly higher GLUT-4 protein concentration and citrate synthase activity than the UT rats in the soleus, plantaris, RG, and WG. Basal plasma membrane GLUT-4 protein concentration of TR rats was 144% above UT rats (P < 0.01). Stimulation by insulin and contraction resulted in a significant increase in plasma membrane GLUT-4 protein concentration in UT rats only. However, plasma membrane GLUT-4 protein concentration in insulin- and contraction-stimulated TR rats remained 53% and 30% greater than that of UT rats, respectively (P < 0.05). Exercise training did not alter basal, insulin-, or contraction-stimulated GLUT-4 functional activity.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Oleic Acid Stimulates Glucose Uptake Into Adipocytes by Enhancing Insulin Receptor Signaling

2014 ◽  
Vol 126 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Ayako Tsuchiya ◽  
Hisao Nagaya ◽  
Takeshi Kanno ◽  
Tomoyuki Nishizaki
Keyword(s):  
Oleic Acid ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Receptor Signaling ◽  
Insulin Receptor Signaling
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