title: T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice.
abstract: OBJECTIVE
  Insulin activates insulin receptor protein tyrosine kinase and downstream phosphatidylinositol-3-kinase (PI3K)/Akt signalling in muscle to promote glucose uptake. The insulin receptor can serve as a substrate for the protein tyrosine phosphatase (PTP) 1B and T cell protein tyrosine phosphatase (TCPTP), which share a striking 74% sequence identity in their catalytic domains. PTP1B is a validated therapeutic target for the alleviation of insulin resistance in type 2 diabetes. PTP1B dephosphorylates the insulin receptor in liver and muscle to regulate glucose homeostasis, whereas TCPTP regulates insulin receptor signalling and gluconeogenesis in the liver. In this study we assessed for the first time the role of TCPTP in the regulation of insulin receptor signalling in muscle.
  
  
  METHODS
  We generated muscle-specific TCPTP-deficient (Mck-Cre;Ptpn2(lox/lox)) mice (Mck, also known as Ckm) and assessed the impact on glucose homeostasis and muscle insulin receptor signalling in chow-fed versus high-fat-fed mice.
  
  
  RESULTS
  Blood glucose and insulin levels, insulin and glucose tolerance, and insulin-induced muscle insulin receptor activation and downstream PI3K/Akt signalling remained unaltered in chow-fed Mck-Cre;Ptpn2(lox/lox) versus Ptpn2(lox/lox) mice. In addition, body weight, adiposity, energy expenditure, insulin sensitivity and glucose homeostasis were not altered in high-fat-fed Mck-Cre;Ptpn2(lox/lox) versus Ptpn2(lox/lox) mice.
  
  
  CONCLUSIONS
  These results indicate that TCPTP deficiency in muscle has no effect on insulin signalling and glucose homeostasis, and does not prevent high-fat diet-induced insulin resistance. Thus, despite their high degree of sequence identity, PTP1B and TCPTP contribute differentially to insulin receptor regulation in muscle. Our results are consistent with the notion that these two highly related PTPs make distinct contributions to insulin receptor regulation in different tissues.
authors: Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia.
authors: K
authors: K
authors: Loh
authors: T L
authors: TL
authors: Merry
authors: S
authors: S
authors: Galic
authors: B J
authors: BJ
authors: Wu
authors: M J
authors: MJ
authors: Watt
authors: S
authors: S
authors: Zhang
authors: Z-Y
authors: ZY
authors: Zhang
authors: B G
authors: BG
authors: Neel
authors: T
authors: T
authors: Tiganis
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009132:Muscles / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D005947:Glucose