Palmitate and inflammatory state additively induce the expression of PTP1B in muscle cells.
The factors responsible for up-regulation of PTP1B, a negative regulator of insulin signaling, in insulin resistance state are not well understood. We performed a series of experiments in C2C12 muscle cells to determine the role of palmitate and an inflammatory state in regulation of PTP1B. Palmitate (0.75mM) induced PTP1B mRNA and protein level only at 16h. The combination of palmitate and macrophages, accompanied by a great increase of TNF-alpha and IL-6 in the culture media, additively caused a higher level of PTP1B protein levels in the muscle. Higher concentrations of palmitate reduced insulin stimulated glucose uptake in myotubes. A specific inhibitor of PTP1B partly increased insulin stimulated glucose uptake in palmitate treated cells. In conclusion, our results showing the additive influence of palmitate and the inflammatory state in the expression of PTP1B imply the involvement of these factors in the overexpression of PTP1B in insulin resistance state. We further provided the evidence suggesting the mediatory role for PTP1B in palmitate induced insulin resistance in myotubes.
Parvaneh
Leila
L
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Islamic Republic of Iran.
Meshkani
Reza
R
Bakhtiyari
Salar
S
Mohammadtaghvaie
Narges
N
Gorganifiruzjaee
Sattar
S
Taheripak
Gholamreza
G
Golestani
Abolfazl
A
Foruzandeh
Mehdi
M
Larijani
Bagher
B
Taghikhani
Mohammad
M
D000818:Animals; D003470:Culture Media / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008264:Macrophages / Q000502:physiology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D010168:Palmitates / Q000378:metabolism* / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
D003470:Culture Media; D016207:Cytokines; D007328:Insulin; D010168:Palmitates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse; D005947:Glucose