| RRC ID |
71714
|
| Author |
Takada M, Sumi M, Maeda A, Watanabe F, Kamiya T, Ishii T, Nakano M, Akagawa M.
|
| Title |
Pyrroloquinoline quinone, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves impaired glucose tolerance in diabetic KK-A(y) mice.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
Insulin resistance is a pathological hallmark of type 2 diabetes mellitus and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling by tyrosine dephosphorylation of insulin receptor, and increased activity and expression of PTP1B is implicated in the pathogenesis of insulin resistance. Therefore, inhibition of PTP1B is anticipated to improve insulin resistance in type 2 diabetic subjects. Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, inhibits PTP1B to oxidatively modify the catalytic cysteine through its redox cycling activity. Here, we report that PQQ induces the ligand-independent activation of insulin signaling by inhibiting cellular PTP1B and enhances glucose uptake through the translocation of glucose transporter 4 in mouse C2C12 myotubes. Furthermore, we demonstrated that oral administration of PQQ improved impaired glucose tolerance in type 2 diabetic KK-A(y) mice. Our results strongly suggest that PQQ can be useful in anti-diabetic treatment for type 2 diabetic subjects.
|
| Volume |
428(2)
|
| Pages |
315-20
|
| Published |
2012-11-16
|
| DOI |
10.1016/j.bbrc.2012.10.055
|
| PII |
S0006-291X(12)02009-8
|
| PMID |
23085227
|
| MeSH |
Animals
Diabetes Mellitus, Experimental / enzymology*
Diabetes Mellitus, Experimental / metabolism
Diabetes Mellitus, Type 2 / enzymology*
Diabetes Mellitus, Type 2 / metabolism
Enzyme Inhibitors / pharmacology*
Glucose Intolerance / enzymology*
Glucose Transporter Type 4 / metabolism
Insulin / metabolism*
Mice
Mice, Inbred Strains
Muscle Fibers, Skeletal / drug effects
Muscle Fibers, Skeletal / enzymology
Muscle Fibers, Skeletal / metabolism
PQQ Cofactor / pharmacology*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Signal Transduction / drug effects
|
| IF |
2.985
|
| Resource |
| Human and Animal Cells |
C2C12(RCB0987) |
