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Development of Diabesity in Mice with Pan‐Neuronal Deletion of Shp2
Author(s) -
Krajewski Stan,
Banares Steven,
Huang Xianshu,
Scadeng Miriam,
Jhala Ulupi S.,
Feng GenSheng,
Zhang Eric E.,
Krajewska Maryla
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1166.3
Subject(s) - diabetes mellitus , hyperinsulinemia , insulin resistance , leptin , medicine , endocrinology , biology , knockout mouse , protein tyrosine phosphatase , obesity , receptor
Obesity and diabetes are increasingly serious health problems. However, molecular mechanisms and neuronal regulatory role in the metabolic disorders are not fully understood. We show here that Shp2, a widely expressed Src homology 2‐containing tyrosine phosphatase, indeed plays a critical role in adult brain controlling food intake, energy balance and metabolism. Conditional mutant mice with Shp2 selectively deleted in neurons, generated by crossing a pan‐neuronal Cre‐line (CRE3) with Shp2flox/flox mice developed obesity and diabetes associated with pathophysiological complications that resemble those encountered in humans, such as hyperglycemia, hyperinsulinemia, hyperleptinemia, insulin and leptin resistance, vasculitis, nephropathy, urinary bladder infections, prostatitis, gastric paresis, and impaired spermatogenesis. This mouse model may help to elucidate molecular mechanisms that lead to diabesity in humans. It also provides a tool to study in vivo complications of uncontrolled diabetes. Supported by the NIH grants: NS36821 for SK and DK73945 to GSF