title: Chromogranin A Regulation of Obesity and Peripheral Insulin Sensitivity.
abstract: Chromogranin A (CgA) is a prohormone and granulogenic factor in endocrine and neuroendocrine tissues, as well as in neurons, and has a regulated secretory pathway. The intracellular functions of CgA include the initiation and regulation of dense-core granule biogenesis and sequestration of hormones in neuroendocrine cells. This protein is co-stored and co-released with secreted hormones. The extracellular functions of CgA include the generation of bioactive peptides, such as pancreastatin (PST), vasostatin, WE14, catestatin (CST), and serpinin. CgA knockout mice (Chga-KO) display: (i) hypertension with increased plasma catecholamines, (ii) obesity, (iii) improved hepatic insulin sensitivity, and (iv) muscle insulin resistance. These findings suggest that individual CgA-derived peptides may regulate different physiological functions. Indeed, additional studies have revealed that the pro-inflammatory PST influences insulin sensitivity and glucose tolerance, whereas CST alleviates adiposity and hypertension. This review will focus on the different metabolic roles of PST and CST peptides in insulin-sensitive and insulin-resistant models, and their potential use as therapeutic targets.
authors.affiliation: Department of Medicine, University of California San Diego , La Jolla, CA , USA.
authors.forename: Gautam K
authors.initials: GK
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Medicine, Metabolic Physiology and Ultrastructural Biology Laboratory, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
keywords: catestatin; chromogranin A knockout; inflammation; insulin resistance; obesity; pancreastatin