title: Islet β-cell failure in type 2 diabetes--Within the network of toxic lipids.
abstract: Obesity-related type 2 diabetes develops in individuals with the onset of β-cell dysfunction. Pancreatic islet lipotoxicity is now recognized as a primary reason for the onset and progression of the disease. Such dysfunction is reflected by the aberrant secretory capacity and detrimental loss of β-cell mass and survival. Elevated circulating serum fatty acid levels and disordered lipid metabolism management are particularly interesting in the search for biologically relevant triggers of β-cell demise. Herein, we review various types of toxic lipid metabolites that may play a significant role in pancreatic islet failure. The lipotoxic effect on β-cells depends on the type of lipid mediator (e.g., long-chain fatty acids, diacylglycerols, ceramides, phospholipids), cellular location of its action (e.g., endoplasmic reticulum, mitochondria), and associated-organelle conditions (e.g., membranes, vesicles). We also discuss various aspects of lipid action in β-cells, including effects on metabolic pathways, stress responses (e.g., oxidative stress, endoplasmic reticulum stress, and autophagy), and gene expression.
authors.affiliation: Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Janikiewicz
authors.affiliation: Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Hanzelka
authors.affiliation: Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kozinski
authors.affiliation: Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kolczynska
authors.affiliation: Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland. Electronic address: adobrzyn@nencki.gov.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dobrzyn
mesh_terms: D001343:Autophagy; D002518:Ceramides / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007515:Islets of Langerhans / Q000503:physiopathology*; D008928:Mitochondria / Q000502:physiology
chemical_list: D002518:Ceramides
keywords: Autophagy; Endoplasmic reticulum stress; Fatty acid-induced toxicity; Mitochondrial dysfunction; Pancreatic β-cell; Type 2 diabetes mellitus