Phosphatase and tensin homolog (PTEN) is most prominently known for its function in tumorigenesis. However, a metabolic role of PTEN is emerging as a result of its altered expression in type 2 diabetes (T2D), which results in impaired insulin signaling and promotion of insulin resistance during the pathogenesis of T2D. PTEN functions in regulating insulin signaling across different organs have been identified. Through the use of a variety of models, such as tissue-specific knockout (KO) mice and in vitro cell cultures, PTEN's role in regulating insulin action has been elucidated across many cell types. Herein, we will review the recent advancements in the understanding of PTEN's metabolic functions in each of the tissues and cell types that contribute to regulating systemic insulin sensitivity and discuss how PTEN may represent a promising therapeutic strategy for treatment or prevention of T2D.
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http://dx.doi.org/10.1101/cshperspect.a036137 | DOI Listing |
Circ Res
January 2025
British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, James Black Centre, King's College London, United Kingdom (C.Y.H., M.-Y.W., J.T., S.A., L.D., G.A., R.H., C.M.S.).
Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.
Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.
Int J Obes (Lond)
January 2025
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston Salem, NC, 27101, USA.
Previous studies have identified G protein-coupled receptor (GPCR) kinase 5 (GRK5) as a genetic factor contributing to obesity pathogenesis, but the underlying mechanism remains unclear. We demonstrate here that Grk5 mRNA is more abundant in stromal vascular fractions of mouse white adipose tissue, the fraction that contains adipose progenitor cells, or committed preadipocytes, than in adipocyte fractions. Thus, we generated a GRK5 knockout (KO) 3T3-L1 preadipocyte to further investigate the mechanistic role of GRK5 in regulating adipocyte differentiation.
View Article and Find Full Text PDFG3 (Bethesda)
January 2025
Department of Biology, Duke University, Durham, NC 27708, USA.
Insulin/IGF signaling (IIS) regulates developmental and metabolic plasticity. Conditional regulation of insulin-like peptide expression and secretion promotes different phenotypes in different environments. However, IIS can also be regulated by other, less-understood mechanisms.
View Article and Find Full Text PDFEndurance exercise is widely recognized for its role in mitigating insulin resistance, yet the precise mechanisms remain unclear. In this Classics in Diabetes article, we revisit the article by Amati et al., "Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance: Another Paradox in Endurance-Trained Athletes?" Published in the October 2011 issue of Diabetes, this article was among the first to highlight the nuanced roles of exercise-induced changes in bioactive lipids such as ceramide and diacylglycerol (DAG) in insulin signaling.
View Article and Find Full Text PDFJ Endocrinol
January 2025
J Shaw, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom of Great Britain and Northern Ireland.
Endocrine dysfunction and diabetes can develop secondary to fibrotic diseases within the pancreas including cystic fibrosis (CF). Phenotypic shift within epithelial cells has been recognised in association with pro-fibrotic signalling. We sought evidence of endocrine cell epithelial-to-mesenchymal transition in CF and non-CF pancreas.
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