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Publication : Insulin receptor signalling in PDGFRβ-expressing cells influences systemic metabolism and negatively impacts lipid storage.

First Author  Warmke N Year  2024
Journal  Biochem Biophys Res Commun Volume  735
Pages  150799 PubMed ID  39406023
Mgi Jnum  J:358455 Mgi Id  MGI:7781037
Doi  10.1016/j.bbrc.2024.150799 Citation  Warmke N, et al. (2024) Insulin receptor signalling in PDGFRbeta-expressing cells influences systemic metabolism and negatively impacts lipid storage. Biochem Biophys Res Commun 735:150799
abstractText  Pericytes are vascular mural cells that support the microvasculature; their dysfunction contributes to diabetic retinopathy and has been linked to obesity in humans. To explore the role of pericyte insulin signalling on systemic metabolism we utilised male mice from our previously described PIR(-/-) (PIRKO) mouse line which has insulin receptor (Insr) knockout in PDGFRbeta-expressing cells. These animals exhibit systemic insulin resistance from as early as 8-weeks of age, despite no change in body weight or activity level, and show altered body composition and hepatosteatosis. When challenged with high fat diet, PIR(-/-) remain insulin resistant but are protected from weight gain with reduced adipose tissue expansion across all depots and altered adipose morphology. Exhibiting parallels with the metabolically-obese-normal-weight (MONW) human phenotype, the PIR(-/-) line underlines the importance of pericyte biology in the development of both diabetes and obesity and establishes the angiopoietin (Ang)/Tie signalling pathway as a focus for future research.
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