Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic OLETF rats

摘要

Streptozotocin (STZ)-induced diabetes has been widely used in rats as an experimental model of type 1 diabetes mellitus, whereas some strains such as Goto-Kakizaki (GK) rats (13) and Zucker diabetic fatty rats (28) are known as models of type 2 diabetes. However, the disease form in most diabetic models is different from human diabetes and diabetic nephropathy, so that the conclusions drawn are not easily transferable. Recently, a new rat strain with type 2 diabetes [Otsuka Long-Evans Tokushima Fatty (OLETF)] has been described that had a similar mature onset of type 2 diabetes mellitus than observed in humans. Because of the closer resemblance to human diabetic nephropathy, we used these rats to assess whether autoregulatory and tubuloglomerular feedback (TGF) responses as suspected underlying mechanisms of diabetic nephropathy are abnormal, and whether such abnormalities precede the onset of type 2 diabetes mellitus.