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.

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.

Emulsification of coenzyme Q10 using gum arabic increases bioavailability in rats and human and improves food-processing suitability.

We evaluated the characteristics of a coenzyme Q(10) (CoQ(10)) formulation created with gum arabic. We defined the formulation's "modulus of inclusion," a reference index of the emulsified state, as the CoQ(10) not extracted by hexane as a percentage of the total CoQ(10) content of the formulation. The emulsified CoQ(10) formulation had a smaller particle size and larger modulus of inclusion value than the equivalent unemulsified formulation. In a kinetic study in rats, serum CoQ(10) levels were significantly greater with the emulsified CoQ(10) formulation than with the equivalent unemulsified formulation, which barely increased the levels. In a human study, oral intake of the emulsified formulation significantly increased plasma CoQ(10) levels, which peaked 6 h after intake, compared with the equivalent unemulsified formulation or CoQ(10) bulk powder. There was a significant positive correlation between baseline plasma CoQ(10) and total cholesterol levels, but no correlation was observed between absorption of CoQ(10) and baseline CoQ(10) levels. The emulsified CoQ(10) formulation was highly stable against heat and high humidity and in the presence of some materials (magnesium oxide, vitamin C, and vitamin E). In conclusion, emulsification of CoQ(10) using gum arabic increased bioavailability in both rats and humans and improved suitability for food processing.