Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

2003 ◽  
Vol 284 (1) ◽  
pp. E47-E54 ◽  
Author(s):  
Agus Suryawan ◽  
Teresa A. Davis
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Tyrosine Phosphorylation ◽  
Insulin Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Age Groups ◽  
Protein Tyrosine Phosphatase 1B ◽  
Neonatal Pigs

The high activity of the insulin-signaling pathway contributes to the enhanced feeding-induced stimulation of translation initiation in skeletal muscle of neonatal pigs. Protein-tyrosine-phosphatase 1B (PTP1B) is a negative regulator of the tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1). The activity of PTP1B is determined mainly by its association with IR and Grb2. We examined the level of PTP1B activity, PTP1B protein abundance, PTP1B tyrosine phosphorylation, and the association of PTP1B with IR and Grb2 in skeletal muscle and liver of fasted and fed 7- and 26-day-old pigs. PTP1B activity in skeletal muscle was lower (P < 0.05) in 7- compared with 26-day-old pigs but in liver was similar in the two age groups. PTP1B abundances were similar in muscle but lower (P < 0.05) in liver of 7- compared with 26-day-old pigs. PTP1B tyrosine phosphorylation in muscle was lower (P < 0.05) in 7- than in 26-day-old pigs. The associations of PTP1B with IR and with Grb2 were lower (P < 0.05) at 7 than at 26 days of age in muscle, but there were no age effects in liver. Finally, in both age groups, fasting did not have any effect on these parameters. These results indicate that basal PTP1B activation is developmentally regulated in skeletal muscle of neonatal pigs, consistent with the developmental changes in the activation of the insulin-signaling pathway reported previously. Reduced PTP1B activation in neonatal muscle likely contributes to the enhanced insulin sensitivity of skeletal muscle in neonatal pigs.

Gliclazide increases insulin receptor tyrosine phosphorylation but not p38 phosphorylation in insulin-resistant skeletal muscle cells

2002 ◽  
Vol 205 (23) ◽  
pp. 3739-3746 ◽  
Author(s):  
Naresh Kumar ◽  
Chinmoy S. Dey
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Tyrosine Phosphorylation ◽  
Insulin Signaling ◽  
Mapk Pathway ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Insulin Resistant ◽  
Resistant Cells

SUMMARY Sulfonylurea drugs are used in the treatment of type 2 diabetes. The mechanism of action of sulfonylureas is to release insulin from pancreatic cells and they have been proposed to act on insulin-sensitive tissues to enhance glucose uptake. The goal of the present study was to test the hypothesis that gliclazide, a second-generation sulfonylurea, could enhance insulin signaling in insulin-resistant skeletal muscle cells. We demonstrated that gliclazide enhanced insulin-stimulated insulin receptor tyrosine phosphorylation in insulin-resistant skeletal muscle cells. Although insulin receptor substrate-1 tyrosine phosphorylation was unaffected by gliclazide treatment, phosphatidylinositol 3-kinase activity was partially restored by treatment with gliclazide. No increase in 2-deoxyglucose uptake in insulin-resistant cells by treatment with gliclazide was observed. Further investigations into the mitogen-activated protein kinase (MAPK) pathway revealed that insulin-stimulated p38 phosphorylation was impaired, as compared with extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase(JNK), which were phosphorylated normally in insulin-resistant cells. Treatment with gliclazide could not restore p38 phosphorylation in insulin-resistant cells. We propose that gliclazide can regulate part of the insulin signaling in insulin-resistant skeletal muscle, and p38 could be a potential therapeutic target for glucose uptake to treat insulin resistance.

scholarly journals Glucose Uptake Stimulatory and PTP1B Inhibitory Activities of Pimarane Diterpenes from Orthosiphon stamineus Benth

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 859 ◽  
Author(s):  
Phi Hung Nguyen ◽  
Huynh Nhu Tuan ◽  
Duc Thuan Hoang ◽  
Quoc Trung Vu ◽  
Minh Quan Pham ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Insulin Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Orthosiphon Stamineus ◽  
Potent Inhibition ◽  
Ic50 Values ◽  
Inhibitory Activities

Seven pimarane diterpenes (1–7) were isolated from Orthosiphon stamineus Benth. by assay-guided isolation. All of the isolates possessed a 2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose uptake effect in 3T3-L1 adipocytes at concentrations of 5 and 10 μM. Most of them showed potent inhibition against protein tyrosine phosphatase 1B with IC50 values ranging from 0.33 to 9.84 μM. In the kinetic study, all inhibition types were exposed for the examined potencies, including mixed-competitive (1), non-competitives (3 and 5), competitive (6), and uncompetitive (7). The results suggested that O. stamineus and its pimarane diterpenes might exert the hypoglycemic effect via the insulin signaling pathway targeting inhibition of protein tyrosine phosphatase 1B (PTP1B) activity.

Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs

2001 ◽  
Vol 281 (5) ◽  
pp. E908-E915 ◽  
Author(s):  
Agus Suryawan ◽  
Hanh V. Nguyen ◽  
Jill A. Bush ◽  
Teresa A. Davis
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Protein ◽  
Neonatal Pigs ◽  
Skeletal Muscle Protein Synthesis ◽  
Primary Determinant

In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a response that declines with development. Both the magnitude of the feeding response and its developmental decline can be reproduced by insulin infusion, suggesting that an altered responsiveness to insulin is a primary determinant of the developmental decline in the stimulation of protein synthesis by feeding. In this study, 7- and 26-day-old pigs were either fasted overnight or fed porcine milk after an overnight fast. We examined the abundance and degree of tyrosine phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and IRS-2 in skeletal muscle and, for comparison, liver. We also evaluated the association of IRS-1 and IRS-2 with phosphatidylinositol 3-kinase (PI 3-kinase). The abundance of IR protein in muscle was twofold higher at 7 than at 26 days, but IRS-1 and IRS-2 abundances were similar in muscle of 7- and 26-day-old pigs. The feeding-induced phosphorylations were greater at 7 than at 26 days of age for IR (28- vs. 13-fold), IRS-1 (14- vs. 8-fold), and IRS-2 (21- vs. 12-fold) in muscle. The associations of IRS-1 and IRS-2 with PI 3-kinase were also increased by refeeding to a greater extent at 7 than at 26 days (9- vs. 5-fold and 6- vs. 4-fold, respectively). In liver, the abundance of IR, IRS-1, and IRS-2 was similar at 7 and 26 days of age. Feeding increased the activation of IR, IRS-1, IRS-2, and PI 3-kinase in liver only twofold, and these responses were unaffected by age. Thus our findings demonstrate that the feeding-induced activation of IR, IRS-1, IRS-2, and PI 3-kinase in skeletal muscle decreases with development. Further study is needed to ascertain whether the developmental decline in the feeding-induced activation of early insulin-signaling components contributes to the developmental decline in translation initiation in skeletal muscle.

Sign in / Sign up

Export Citation Format

Share Document