Cited by 72Regulation of Appetite and ObesityProtein Tyrosine PhosphatasesAdipokines, Inflammation, and Metabolic Diseases

Development of Diabesity in Mice with Neuronal Deletion of Shp2 Tyrosine Phosphatase

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Krajewska, Maryla, Banares, Steven, Zhang, Eric E., Huang, Xianshu, Scadeng, Miriam, Jhala, Ulupi S., Feng, Gen-Sheng, Krajewski, Stan·2008·The American Journal of Pathology

Abstract

Obesity and diabetes, termed "diabesity," are serious health problems that are increasing in frequency. However, the molecular mechanisms and neuronal regulation of these metabolic disorders are not fully understood. We show here that Shp2, a widely expressed Src homology 2-containing Tyr phosphatase, plays a critical role in the adult brain to control food intake, energy balance, and metabolism. Mice with a neuron-specific, conditional Shp2 deletion were generated by crossing a pan-neuronal Cre-line (CRE3) with Shp2(flox/flox) mice. These congenic mice, CRE3/Shp2-KO, developed obesity and diabetes and the associated pathophysiological complications that resemble those encountered in humans, including hyperglycemia, hyperinsulinemia, hyperleptinemia, insulin and leptin resistance, vasculitis, diabetic nephropathy, urinary bladder infections, prostatitis, gastric paresis, and impaired spermatogenesis. This mouse model may help to elucidate the molecular mechanisms that lead to the development of diabesity in humans and provide a tool to study the in vivo complications of uncontrolled diabetes.

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  • Neuronal deletion of SHP2 signalling in mice led to hyperphagia, severe obesity, and glucose dysregulation.

    “Neuronal deletion of SHP2 signalling in mice led to hyperphagia, severe obesity and glucose dysregulation145.”

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Research works printed but not linked: 2

  1. Gerich JE, Gosmanov N: Atlas of Diabetes: Pathogenesis of Type 2 Diabetes. Edited by JS Skyler. Philadelphia, PA, Lippincott Williams & Wilkins, 2002, pp 78 -82
  2. Lai LA, Zhao C, Zhang EE, Feng GS: The Shp-2 Tyrosine Phospha- tase. Edited by JA Arino. Berlin, Springer-Verlag, 2004, pp 275-299

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Authors
Krajewska, M., Banares, S., Zhang, E. E., Huang, X., Scadeng, M., Jhala, U. S., Feng, G.-S., & Krajewski, S.
Affiliations
  • Sanford Burnham Prebys Medical Discovery Institute (US)
  • University of California San Diego (US)
Corresponding author
  • Feng, Gen-Sheng
  • Krajewski, Stan
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2008-05
Volume
172
Issue
5
Pages
1312-1324
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2043625750
Cited by
72
References
40
Citations by year
2024: 3 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 5 · 2016: 4 · 2015: 5 · 2014: 8 · 2013: 11 · 2012: 12
FWCI
1.78
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK73945, R01DK073945)
  • National Institute of Neurological Disorders and Stroke (R01NS036821, NS 36821)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
SHP2, diabesity, obesity, diabetes mellitus, conditional knockout mice, dietary intake, energy balance, insulin resistance, leptin resistance, hyperinsulinemia, hyperleptinemia, diabetic nephropathy, vasculitis, cystitis, prostatitis, spermatogenesis
MeSH terms
Animals, Crosses, Genetic, Diabetes Mellitus, Eating, Female, Hyperglycemia, Hyperinsulinism, Insulin Resistance, Male, Mice, Mutant Strains, Mice, Transgenic, Neurons, Obesity, Signal Transduction, Leptin, Diabetes Complications, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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