Development of Diabesity in Mice with Neuronal Deletion of Shp2 Tyrosine Phosphatase
Open accessAbstract
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.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [145]
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Shpakov, A. O. (2016) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093016030017 · Cited by 11 · see citing works
Protein Tyrosine Phosphatases in Metabolism: A New Frontier for Therapeutics
Bennett, A. M., & Tiganis, T. (2024) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022724-105540 · Cited by 12 · see citing works
Zhao, Z., Bai, Y., Tian, H., Shi, B., Li, X., Luo, Y., Wang, J., Hu, J., & Raza, S. H. A. (2021) · Genomics · doi:10.1016/j.ygeno.2021.09.020 · Cited by 11 · see citing works
The Tyrosine Phosphatase SHP2: A New Target for Insulin Resistance?
Saint-Laurent, C., Mazeyrie, L., Tajan, M., Paccoud, R., Castan‐Laurell, I., Valet, P., Édouard, T., Pradère, J., Dray, C., & Yart, A. (2022) · Biomedicines · doi:10.3390/biomedicines10092139 · Cited by 11 · see citing works
Effects of Noonan Syndrome-Germline Mutations on Mitochondria and Energy Metabolism
Bajia, D., Bottani, E., & Derwich, K. (2022) · Cells · doi:10.3390/cells11193099 · Cited by 10 · see citing works
Polymorphisms of PTPN11 gene could influence serum lipid levels in a sex-specific pattern
Jia, Z., Cao, X., Cao, D., Kong, F., Kharbuja, P., & Jiang, J. (2013) · Lipids in Health and Disease · doi:10.1186/1476-511x-12-72 · Cited by 10 · see citing works
Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells
Vignozzi, L., Cellai, I., Santi, R., Lombardelli, L., Morelli, A., Comeglio, P., Filippi, S., Logiodice, F., Carini, M., Nesi, G., et al. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0142e · Cited by 10 · see citing works
The Cell-Specific Role of SHP2 in Regulating Bone Homeostasis and Regeneration Niches
Zhang, J., Ye, C., Zhu, Y., Wang, J., & Liu, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032202 · Cited by 8 · see citing works
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Metabolic Syndrome and LUTS/BPH
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SHP2 : une cible potentielle d’intérêt dans l’obésité et ses complications métaboliques ?
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Leptin, the Autonomic Nervous System, and Hypertension
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Protein Tyrosine Phosphatase Epsilon as a Regulator of Body Weight and Glucose Metabolism
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SHP2/PTPN11 PROTEIN-TYROSINE PHOSPHATASE PROMOTES MAST CELL HOMEOSTASIS AND SYSTEMIC MASTOCYTOSIS
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Self-citation
- 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)
- PMC
- PMC2329840
- 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
- bronze
- doi.org
- 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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