T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice

K. Loh, T. L. Merry, S. Galic, B. J. Wu, M. J. Watt, S. Zhang, Zhong-Yin Zhang, B. G. Neel, T. Tiganis

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Aims/hypothesis: 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/interpretation: 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.

Original languageEnglish
Pages (from-to)468-478
Number of pages11
JournalDiabetologia
Volume55
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Non-Receptor Type 2 Protein Tyrosine Phosphatase
Insulin Receptor
Homeostasis
Insulin
Glucose
Muscles
Phosphatidylinositol 3-Kinase
Insulin Resistance
Fats
Non-Receptor Type 1 Protein Tyrosine Phosphatase
Gluconeogenesis
Liver
Adiposity
High Fat Diet
Type 2 Diabetes Mellitus
Energy Metabolism
Blood Glucose
Catalytic Domain

Keywords

  • Diabetes
  • Glucose homeostasis
  • Insulin resistance
  • Insulin signalling
  • Muscle
  • Protein tyrosine phosphatase
  • PTP
  • PTP1B
  • TCPTP

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice. / Loh, K.; Merry, T. L.; Galic, S.; Wu, B. J.; Watt, M. J.; Zhang, S.; Zhang, Zhong-Yin; Neel, B. G.; Tiganis, T.

In: Diabetologia, Vol. 55, No. 2, 02.2012, p. 468-478.

Research output: Contribution to journalArticle

Loh, K. ; Merry, T. L. ; Galic, S. ; Wu, B. J. ; Watt, M. J. ; Zhang, S. ; Zhang, Zhong-Yin ; Neel, B. G. ; Tiganis, T. / T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice. In: Diabetologia. 2012 ; Vol. 55, No. 2. pp. 468-478.
@article{e15873f6734b4fc08be3341acf4c61e1,
title = "T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice",
abstract = "Aims/hypothesis: 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/interpretation: 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.",
keywords = "Diabetes, Glucose homeostasis, Insulin resistance, Insulin signalling, Muscle, Protein tyrosine phosphatase, PTP, PTP1B, TCPTP",
author = "K. Loh and Merry, {T. L.} and S. Galic and Wu, {B. J.} and Watt, {M. J.} and S. Zhang and Zhong-Yin Zhang and Neel, {B. G.} and T. Tiganis",
year = "2012",
month = "2",
doi = "10.1007/s00125-011-2386-z",
language = "English",
volume = "55",
pages = "468--478",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice

AU - Loh, K.

AU - Merry, T. L.

AU - Galic, S.

AU - Wu, B. J.

AU - Watt, M. J.

AU - Zhang, S.

AU - Zhang, Zhong-Yin

AU - Neel, B. G.

AU - Tiganis, T.

PY - 2012/2

Y1 - 2012/2

N2 - Aims/hypothesis: 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/interpretation: 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.

AB - Aims/hypothesis: 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/interpretation: 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.

KW - Diabetes

KW - Glucose homeostasis

KW - Insulin resistance

KW - Insulin signalling

KW - Muscle

KW - Protein tyrosine phosphatase

KW - PTP

KW - PTP1B

KW - TCPTP

UR - http://www.scopus.com/inward/record.url?scp=84856691770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856691770&partnerID=8YFLogxK

U2 - 10.1007/s00125-011-2386-z

DO - 10.1007/s00125-011-2386-z

M3 - Article

VL - 55

SP - 468

EP - 478

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 2

ER -