RGD Reference Report - Deficiency of phosphoinositide 3-kinase enhancer protects mice from diet-induced obesity and insulin resistance. - Rat Genome Database

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Deficiency of phosphoinositide 3-kinase enhancer protects mice from diet-induced obesity and insulin resistance.

Authors: Chan, Chi Bun  Liu, Xia  Jung, Dae Young  Jun, John Y  Luo, Hongbo R  Kim, Jason K  Ye, Keqiang 
Citation: Chan CB, etal., Diabetes. 2010 Apr;59(4):883-93. doi: 10.2337/db09-1404. Epub 2010 Jan 12.
RGD ID: 13838849
Pubmed: PMID:20068140   (View Abstract at PubMed)
PMCID: PMC2844836   (View Article at PubMed Central)
DOI: DOI:10.2337/db09-1404   (Journal Full-text)


OBJECTIVE: Phosphoinositide 3-kinase enhancer A (PIKE-A) is a proto-oncogene that promotes tumor growth and transformation by enhancing Akt activity. However, the physiological functions of PIKE-A in peripheral tissues are unknown. Here, we describe the effect of PIKE deletion in mice and explore the role of PIKE-A in obesity development.
RESEARCH DESIGN AND METHODS: Whole-body PIKE knockout mice were generated and subjected to high-fat-diet feeding for 20 weeks. The glucose tolerance, tissue-specific insulin sensitivity, adipocyte differentiation, and lipid oxidation status were determined. The molecular mechanism of PIKE in the insulin signaling pathway was also studied.
RESULTS: We show that PIKE-A regulates obesity development by modulating AMP-activated protein kinase (AMPK) phosphorylation. PIKE-A is important for insulin to suppress AMPK phosphorylation. The expression of PIKE-A is markedly increased in adipose tissue of obese mice, whereas depletion of PIKE-A inhibits adipocyte differentiation. PIKE knockout mice exhibit a prominent phenotype of lipoatrophy and are resistant to high-fat diet-induced obesity, liver steatosis, and diabetes. PIKE knockout mice also have augmented lipid oxidation, which is accompanied by enhanced AMPK phosphorylation in both muscle and adipose tissue. Moreover, insulin sensitivity is improved in PIKE-A-deficient muscle and fat, thus protecting the animals from diet-induced diabetes.
CONCLUSIONS: Our results suggest that PIKE-A is implicated in obesity and associated diabetes development by negatively regulating AMPK activity.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
obesity  ISOAgap2 (Mus musculus)13838849; 13838849 RGD 
obesity  IMP 13838849 RGD 
type 2 diabetes mellitus  ISOAgap2 (Mus musculus)13838849; 13838849 RGD 
type 2 diabetes mellitus  IMP 13838849 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agap2  (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2)

Genes (Mus musculus)
Agap2  (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2)

Genes (Homo sapiens)
AGAP2  (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2)


Additional Information