Sweet Killing in Obesity and Diabetes: The Metabolic Role of the BH3-only Protein BIM. Issue 18 (14th September 2018)

• Record Type: Journal Article
• Authors: Miani, Michela; Elvira, Bernat; Gurzov, Esteban N.
• Is Part Of: Journal of molecular biology. Volume 430:Issue 18(2018)Part B
• Page Start: 3041
• Page End: 3050
• Publication Date: 2018-09-14
• Subjects: T1D type 1 diabetes -- T2D type 2 diabetes -- BH3 BCL-2 homology 3 -- ER endoplasmic reticulum -- BIM BCL-2 Interacting Mediator of cell death -- THBS1 thrombospondin 1 -- MANF mesencephalic astrocyte-derived neurotrophic factor -- PTPN2 protein tyrosine phosphatase non-receptor type 2 -- USP18 ubiquitin-specific peptidase 18 -- GLIS3 GLIS family zinc finger 3 -- CTSH cathepsin H -- BACH2 BTB domain and CNC homolog 2 -- Treg regulatory T cells -- FoxP3 Forkhead box P3 -- Pdx1 pancreatic duodenal homeobox-1 -- ROS reactive oxygen species -- FoxO3A Forkhead box O3a -- Keap-1 Kelch-like ECH-associated protein-1 -- PKR protein kinase R -- CEBP/δ CCAAT/enhancer binding protein δ -- IRS2 insulin receptor substrate 2 -- CHOP C/ERB homologous protein -- Mst1 mammalian sterile 20-like kinase 1 -- DLC1 dynein light chain 1 -- BLKO BIM liver-specific knockout; BIM -- BH3-only proteins -- apoptosis -- type 1 diabetes -- type 2 diabetes; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.07.022
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Diabetes is a metabolic disorder affecting more than 400 million individuals and their families worldwide. The major forms of diabetes (types 1 and 2) are characterized by pancreatic β-cell dysfunction and, in some cases, loss of β-cell mass causing hyperglycemia due to absolute or relative insulin deficiency. The BCL-2 homology 3 (BH3)-only protein BIM has a wide role in apoptosis induction in cells. In this review, we describe the apoptotic mechanisms mediated by BIM activation in β cells in obesity and both forms of diabetes. We focus on molecular pathways triggered by inflammation, saturated fats, and high levels of glucose. Besides its role in cell death, BIM has been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism in hepatocytes. BIM is both a key mediator of pancreatic β-cell death and hepatic insulin resistance and is thus a potential therapeutic target for novel anti-diabetogenic drugs. We consider the implications and challenges of targeting BIM in the treatment of the disease. Graphical Abstract: Unlabelled Image Highlights: BIM is a crucial mediator of pro-inflammatory cytokine-induced β-cell apoptosis in autoimmune diabetes. Pancreatic islets from human organ donors with type 2 diabetes have high expression of BIM. BIM regulates apoptotic pathways of cell death and mitochondrial function in hepatocytes. BIM is a promising drug target for the treatment of obesity and diabetes.