title: SHIP2: a "new" insulin pathway target for aging research.
abstract: Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolic syndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular disease, as well as Alzheimer's disease (AD), all characterized by chronic inflammatory status. On the other hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulin pathway because its over-expression causes impairment of insulin/IGF-1 signaling. Because some single-nucleotide polymorphisms (SNP) of the gene encoding SHIP2 were significantly associated in T2DM patients with metabolic syndrome and some related conditions, we decided to conduct a case-control study on this gene, analyzing AD and T2DM subjects as cases and young, old, and centenarians as controls. Our results suggest a putative correlation between the the rs144989913 SNP and aging, both successful and unsuccessful, rather than age-related diseases. Because this SNP is an insertion/deletion of 28 bp, it might cause an alteration in SHIP2 expression. It is noteworthy that SHIP2 has been demonstrated to be a potent negative regulator of insulin signaling and insulin sensitivity. Many studies demonstrated the association of the insulin/IGF1 pathway with aging and longevity, so it is tempting to speculate that the found association with SHIP2 and aging might depend on its effect on the insulin/IGF-1 pathway.
authors: 1 Immunosenescence Unit, Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo , Palermo, Italy .
authors: Giulia
authors: G
authors: Accardi
authors: Claudia
authors: C
authors: Virruso
authors: Carmela Rita
authors: CR
authors: Balistreri
authors: Fabrizio
authors: F
authors: Emanuele
authors: Federico
authors: F
authors: Licastro
authors: Roberto
authors: R
authors: Monastero
authors: Elisa
authors: E
authors: Porcellini
authors: Sonya
authors: S
authors: Vasto
authors: Salvatore
authors: S
authors: Verga
authors: Calogero
authors: C
authors: Caruso
authors: Giuseppina
authors: G
authors: Candore
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D007328:Insulin / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012106:Research; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D007328:Insulin; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases