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Insulin and IGF-I phosphorylate eNOS in HUVECs by a caveolin-1 dependent mechanism.
No full textCaveolae are plasmamembrane regions which take part in the regulation of intracellular trafficking and signaling of tyrosine kinase receptors. Insulin and IGF-I receptors and their intracellular substrates localize in caveolae. Also eNOS is targeted to caveolae and caveolin-1, the major caveolar protein, acts as a regulator of eNOS activity. Since Insulin and IGF-I phosphorylate and activate eNOS, we investigated the role of caveolin-1 in Insulin and IGF-I stimulated eNOS activity. Here we show that: (1) in human endothelial cells, Insulin and IGF-I stimulate eNOS phosphorylation in a different manner both qualitatively and quantitatively; (2) caveolin-1 down regulation abolishes Insulin and IGF-I stimulated eNOS phosphorylation. These results suggest that caveolae could represent an intracellular site that contributes to differentiate IR and IGF-IR activity, and demonstrate the role of caveolin-1 in the eNOS activation by Insulin and IGF-I
Caveolin-1 and polymerase I and transcript release factor: new players in insulin-like growth factor-I receptor signaling.
No full textBeta-cell function improvement after biliopancreatic diversion in subjects withtype 2 diabetes and morbid obesity.
No full textIn subjects with obesity and type 2 diabetes mellitus (T2DM), biliopancreatic
diversion (BPD) improves glucose stimulated insulin secretion, whereas the
effects on other secretion mechanisms are still unknown. Our objective was to
evaluate the early effects of BPD on nonglucose-stimulated insulin secretion. In
16 morbid obese subjects (9 with T2DM and 7 with normal fasting glucose (NFG)),
we measured insulin secretion after glucose-dependent arginine stimulation test
and after intravenous glucose tolerance test (IVGTT) before and 1 month after
BPD. After surgery the mean weight lost was 13% in both groups. The acute insulin
response during IVGTT was improved in T2DM after BDP (from 55 +/- 10 to 277 +/-
91 pmol/l, P = 0.03). A reduction of insulin response to arginine was observed in
NFG, whereas opposite was found in T2DM. In particular, acute insulin response to
arginine at basal glucose concentrations (AIR(basal)) was reduced but insulin
response at 14 mmol/l of plasma glucose (AIR(14)) was increased. Therefore, after
BPD any statistical difference in AIR(14) between NFG and T2DM disappeared (1,032
+/- 123 for NFG and 665 +/- 236 pmol/l for T2DM, P = ns). The same was observed
for Slope(AIR), a measure of glucose potentiation, reduced in T2DM before BPD but
increased after surgery, when no statistically significant difference resulted
compared with NFG (Slope(AIR) after BPD: 78 +/- 11 in NFG and 56 +/- 18 pmol/l in
T2DM, P = ns). In conclusion, in obese T2DM subjects 1 month after BPD we
observed a great improvement of both glucose- and nonglucose-stimulated insulin
secretions. The mechanisms by which BDP improve insulin secretion are still
unknown
high molecular weight adiponectin isoforms increase after bilopancreati diversion in obese subjects
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Caveolin-1 down-regulation inhibits insulin-like growth factor-I receptor signal transduction in H9C2 rat cardiomyoblasts.
No full textCaveolin (Cav)-1, the major caveolar protein, directly interacts with IGF-I receptor (IGF-IR) and its intracellular substrates. To determine the role of Cav-1 in IGF-IR signaling, we transfected H9C2 cells with small interfering RNA specific for Cav-1-siRNA. The selective down-regulation of Cav-1 (90%) was associated with a smaller reduction of Cav-2, whereas Cav-3 expression was unaffected. A significant reduction of IGF-IR tyrosine phosphorylation in Cav-1-siRNA H9C2 cells was found compared with H9C2 control cells (Ctr-siRNA). The reduced IGF-IR autophosphorylation resulted in a decrease of insulin receptor substrate-1, Shc, and Akt activation. In addition, in Cav-1-siRNA H9C2 cells, IGF-I did not prevent apoptosis, suggesting that Cav-1 is required to mediate the antiapoptotic effect of IGF-I in cardiomyoblasts. The down-regulation of Cav-1 decreased IGF-IR activation and affected the ability of IGF-I to prevent apoptosis after serum withdrawal also in human umbilical vein endothelial cells. These results demonstrate that: 1) Cav-1 down-regulation negatively affects IGF-IR tyrosine phosphorylation; 2) this effect causes a reduced activation of insulin receptor substrate-1, Shc, and Akt; and 3) Cav-1 is involved in IGF-IR antiapoptotic signaling after serum deprivation
The signature motif in human glucose-6-phosphate transporter is essential for microsomal transport of glucose-6-phosphate.
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