Protein Tyrosine Phosphatases in Hypothalamic Insulin and Leptin Signaling

Zhong-Yin Zhang, Garron T. Dodd, Tony Tiganis

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The hypothalamus is critical to the coordination of energy balance and glucose homeostasis. It responds to peripheral factors, such as insulin and leptin, that convey to the brain the degree of adiposity and the metabolic status of the organism. The development of leptin and insulin resistance in hypothalamic neurons appears to have a key role in the exacerbation of diet-induced obesity. In rodents, this has been attributed partly to the increased expression of the tyrosine phosphatases Protein Tyrosine Phosphatase 1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP), which attenuate leptin and insulin signaling. Deficiencies in PTP1B and TCPTP in the brain, or specific neurons, promote insulin and leptin signaling and prevent diet-induced obesity, type 2 diabetes mellitus (T2DM), and fatty liver disease. Although targeting phosphatases and hypothalamic circuits remains challenging, recent advances indicate that such hurdles might be overcome. Here, we focus on the roles of PTP1B and TCPTP in insulin and leptin signaling and explore their potential as therapeutic targets.

Original languageEnglish (US)
Pages (from-to)661-674
Number of pages14
JournalTrends in Pharmacological Sciences
Volume36
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

Protein Tyrosine Phosphatases
Non-Receptor Type 2 Protein Tyrosine Phosphatase
Leptin
Non-Receptor Type 1 Protein Tyrosine Phosphatase
Insulin
Nutrition
Neurons
Brain
Obesity
Diet
Phosphatases
Adiposity
Fatty Liver
Medical problems
Energy balance
Phosphoric Monoester Hydrolases
Liver
Type 2 Diabetes Mellitus
Hypothalamus
Tyrosine

Keywords

  • hypothalamus
  • insulin
  • leptin
  • obesity
  • protein tyrosine phosphatases
  • type 2 diabetes

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Protein Tyrosine Phosphatases in Hypothalamic Insulin and Leptin Signaling. / Zhang, Zhong-Yin; Dodd, Garron T.; Tiganis, Tony.

In: Trends in Pharmacological Sciences, Vol. 36, No. 10, 01.10.2015, p. 661-674.

Research output: Contribution to journalArticle

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