An enigma: does a high-protein diet accelerate renal damage in humans? Lessons from diabetic animal models

摘要

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease worldwide. For decades, substantial efforts have been made to study the pathogenesis of DN, develop potential diagnostic biomarkers to evaluate the disease progression, and formulate potential therapeutic medications. All these endeavors were carried out and validated in animal models before their deployment in humans. Therefore, it seems that the establishment and utilization of reliable murine models that recapitulate human DN characteristics is critical for the success of translational diagnostic and therapeutic studies. In this regard, the Animal Models of Diabetic Complications Consortium was initiated by the National Institutes of Health more than a decade ago to set up the criteria for qualified DN animal models encompassing various criteria, including blood glucose, albuminuria, glomerular filtration rate (GFR), and renal histopathology (2). Accordingly, a series of murine models has hence been identified that are widely used in DN research. Based on different types of diabetes, standard type 1 diabetic models, such as streptozotocin-induced diabetic mice, insulin-2 Akita mutant mice, and OVE26 mice with calmodulin gene mutation, were identified. Commonly used type 2 diabetes mellitus (T2DM) models included high-fat diet-induced diabetic mice as well as ob/ob and db/db mice with genetic defects in leptin (ob/ob) or the leptin receptor (db/db) on the C57BLKS background (1, ).