The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2
Jennifer M Dyson1, Anne M Kong, Fenny Wiradjaja
1Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Vic. 3800, Australia.
The International Journal of Biochemistry & Cell Biology
|June 21, 2005
Summary
The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) enzyme plays a role in obesity and type 2 diabetes. New research shows SHIP2 gene inactivation in mice prevents obesity, suggesting it
Area of Science:
- Cellular signaling and metabolism
- Molecular biology and genetics
Background:
- Phosphoinositides are key signaling molecules regulating vital cellular processes like apoptosis, proliferation, and insulin signaling.
- The enzyme SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), impacting phosphoinositide 3-kinase (PI3K) signaling.
- SHIP2 gene polymorphisms are linked to type 2 diabetes mellitus in human studies.
Purpose of the Study:
- To investigate the role of SHIP2 in metabolic regulation, specifically in the context of obesity and insulin sensitivity.
- To clarify conflicting results from previous genetic ablation studies of SHIP2 in mice.
Main Methods:
- Generation of a novel SHIP2 knockout mouse model with intact Phox2a gene.
- Assessment of insulin and glucose tolerance in the knockout mice.
- Evaluation of weight gain and obesity resistance on high-fat diets.
Main Results:
- Mice lacking functional SHIP2 exhibited normal insulin and glucose tolerance.
- These SHIP2 knockout mice demonstrated significant resistance to weight gain when fed a high-fat diet, displaying an obesity-resistant phenotype.
- The results contrast with earlier studies that reported lethal hypoglycemia due to confounding genetic deletions.
Conclusions:
- SHIP2 plays a critical role in regulating body weight and obesity development.
- SHIP2 is a promising therapeutic target for managing obesity and type 2 diabetes mellitus.
- Precise genetic models are crucial for understanding complex gene functions and their physiological impact.
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