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AdipoR3, a member of the adiponectin receptor family expressed in pancreatic beta cells
L.J. Góñez, G. Naselli, L.C. Harrison, in collaboration with H. Niwa, Takasago Research Laboratories Research Institute, Kaneka Corporation, Japan
The adipokine polypeptide, adiponectin, is a key metabolic regulator with anti-diabetic and anti-atherogenic properties. Circulating levels of adiponectin are reduced in humans with visceral obesity, insulin resistance and type 2 diabetes. Furthermore, adiponectin has recently been shown to partially protect rat insulinoma INS-1 cells from fatty acid- and cytokine-induced apoptosis. Two receptors, AdipoR1 and R2, have been identified for the globular form of adiponectin and another receptor, T-cadherin, for a multimeric, high-molecular-weight form of adiponectin. We identified AdipoR3, a member of the AdipoR family, in a screen for genes expressed in pancreatic beta cells. AdipoR3 is tissue-restricted compared to the other adiponectin receptors and in the pancreas is expressed exclusively in beta cells. AdipoR3 has a predicted molecular mass of 29kDa, comprises seven transmembrane domains and is structurally homologous to AdipoR1 and R2 with an intracellular N-terminus and an extracellular C-terminus. However, unlike AdipoR1 and R2, AdipoR3 has an N-terminal mitochondrial targeting sequence and the native protein localizes to mitochondria (Figure 1). AdipoR3 maps to mouse chromosome 5 and human chromosome 7p22.2, a chromosomal region identified by genome-wide scans to harbor type 2 diabetes susceptibility genes. This finding of a novel adiponectin receptor in the beta cell provides a possible insight into the molecular mechanism by which adiponectin confers protection on b cells from cytokine- and fatty acid-induced apoptosis.
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