Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene

M Elchebly, P Payette, E Michaliszyn, W Cromlish… - Science, 1999 - science.org
M Elchebly, P Payette, E Michaliszyn, W Cromlish, S Collins, AL Loy, D Normandin, A Cheng…
Science, 1999science.org
Protein tyrosine phosphatase–1B (PTP-1B) has been implicated in the negative regulation
of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded
healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower
and concentrations of circulating insulin that were one-half those of their PTP-1B+/+
littermates. The enhanced insulin sensitivity of the PTP-1B−/− mice was also evident in
glucose and insulin tolerance tests. The PTP-1B−/− mice showed increased phosphorylation …
Protein tyrosine phosphatase–1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B−/− mice was also evident in glucose and insulin tolerance tests. The PTP-1B−/− mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B−/− and PTP-1B+/− mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.
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