Protein tyrosine phosphatase-1B in diabetes.
A role for protein tyrosine phosphatases in the negative regulation of insulin signaling and a putative involvement in the insulin resistance associated with type 2 diabetes have been postulated since their discovery. The recent demonstration that mice lacking the protein tyrosine phosphatase-1B (PTP-1B) have enhanced insulin sensitivity validates this. Furthermore, when fed a high fat diet, these mice maintained insulin sensitivity and were resistant to obesity, suggesting that inhibition of PTP-1B activity could be a novel way of treating type 2 diabetes and obesity. This commentary reviews our current knowledge of PTP-1B in insulin signaling and its role in diabetes and discusses the development of potent and selective PTP-1B inhibitors.
Kennedy
B P
BP
Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, Pointe Claire-Dorval, H9R 4P8, Quebec, Canada. brian_kennedy@merck.com
Ramachandran
C
C
D000818:Animals; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D051379:Mice; D009765:Obesity; D010641:Phenotype; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism
D011972:Receptor, Insulin; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse