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