New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes.

Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy

“…Expression of mRNA of SREBP-1c, SREBP-2, and ChREBP and their target lipogenesis enzymes was downregulated in human DN, unlike the fi ndings in rodent models ( 39 ), where only early manifestations of DN occur ( 45 ). Changes that we observed in the diabetic human kidney did not always parallel data from animal models; these differences could be due to the fact that changes seen in the human kidney represent much prolonged exposure to the diabetic environment, but it is still possible that in the early stage of hyperglycemia there is increased denovo lipogenesis in the kidney.…”

The ameliorative potential of Hyphaene thebaica on streptozotocin-induced diabetic nephropathy

“…50 rats were divided into the following five groups of ten rats each: -group I (the control group): received 0.1 M citrate buffer pH (4.5) for 6 weeks [29]; -group II: received Hyphaene thebaica extract 150 mg/kg BW by oral gavage for 6 weeks [1]; -group III (DN group): included diabetic nephropathy without treatment; -group IV (prophylactic group): diabetic rats received the same dose of Hyphaene thebaica extract orally for 6 weeks immediately after being diagnosed as diabetic as a protective against the consequences of diabetes, including nephropathy; -group V (curative group): diabetic rats received the same dose of Hyphaene thebaica orally for 3 weeks upon being diagnosed with nephropathy at the 4th week [6,40]. Sample collection.…”

Monitoring p53 by MDM2 and MDMX is required for endocrine pancreas development and function in a spatio-temporal manner

“…Diabetic nephropathy (DN) is a secondary complication of both type 1 and type 2 diabetes and the most common cause of end-stage renal disease in the western world (Chawla et al, 2010; Saran et al, 2015), which is pathologically characterized by glomerular hypertrophy, increased mesangial intercapillary matrix, progressive thickening of the glomerular capillary walls, Kimmelstiel- Wilson nodules distributed in the glomeruli that are the “virtually” pathognomonic of DN, and global glomerulosclerosis at the advanced stage (Betz and Conway, 2014; Soler et al, 2012). A number of animal models have been developed to provide valuable information for studying the pathogenesis, progression, involved signaling pathways, and potential therapeutic approaches of DN (Betz and Conway, 2014, 2016; Breyer et al, 2005; Kaur et al, 2014; Soler et al, 2012).…”