BACKGROUND: Rhesus monkeys have a high prevalence of obesity and spontaneous type 2 diabetes mellitus after the age of 10 years. These monkeys go through a defined, sequential set of metabolic phases, including fasting hyperinsulinemia, impaired glucose tolerance, and fasting hyperglycemia. Using these monkeys, we addressed the hypothesis that renal structural features characteristic of diabetic nephropathy might precede the appearance of overt diabetes. METHODS: We carried out a quantitative analysis of renal tissue, using light microscopy and electron microscopy, from 6 metabolically normal young monkeys, 7 metabolically normal aged monkeys, 7 hyperinsulinemic monkeys, and 18 diabetic monkeys. RESULTS: Glomerular volume was increased significantly in hyperinsulinemic monkeys and diabetic monkeys compared with aged normal monkeys. In the normal monkey, glomerular basement membrane (GBM) width rises with age but reaches a plateau at about 20 years of age; the presence of diabetes was associated with markedly increased GBM width. Glomerular tuft volume and GBM width were correlated most closely with age and with glucose tolerance. CONCLUSION: Diabetic monkey kidneys are characterized by glomerular enlargement, glomerulosclerosis, and thickening of the GBM. Glomerular hypertrophy begins in the prediabetic hyperinsulinemic phase. This finding suggests that early intervention may be required in human patients to preserve normal glomerular structure. Copyright 2002 by the National Kidney Foundation, Inc.
BACKGROUND:Rhesus monkeys have a high prevalence of obesity and spontaneous type 2 diabetes mellitus after the age of 10 years. These monkeys go through a defined, sequential set of metabolic phases, including fasting hyperinsulinemia, impaired glucose tolerance, and fasting hyperglycemia. Using these monkeys, we addressed the hypothesis that renal structural features characteristic of diabetic nephropathy might precede the appearance of overt diabetes. METHODS: We carried out a quantitative analysis of renal tissue, using light microscopy and electron microscopy, from 6 metabolically normal young monkeys, 7 metabolically normal aged monkeys, 7 hyperinsulinemic monkeys, and 18 diabetic monkeys. RESULTS: Glomerular volume was increased significantly in hyperinsulinemic monkeys and diabetic monkeys compared with aged normal monkeys. In the normal monkey, glomerular basement membrane (GBM) width rises with age but reaches a plateau at about 20 years of age; the presence of diabetes was associated with markedly increased GBM width. Glomerular tuft volume and GBM width were correlated most closely with age and with glucose tolerance. CONCLUSION:Diabetic monkey kidneys are characterized by glomerular enlargement, glomerulosclerosis, and thickening of the GBM. Glomerular hypertrophy begins in the prediabetic hyperinsulinemic phase. This finding suggests that early intervention may be required in humanpatients to preserve normal glomerular structure. Copyright 2002 by the National Kidney Foundation, Inc.
Authors: Jiong Zhang; Kim M Hansen; Jeffrey W Pippin; Alice M Chang; Yoshinori Taniguchi; Ronald D Krofft; Scott G Pickering; Zhi-Hong Liu; Christine K Abrass; Stuart J Shankland Journal: Am J Physiol Renal Physiol Date: 2011-11-30
Authors: Victor G Puelles; Rebecca N Douglas-Denton; Luise A Cullen-McEwen; Jinhua Li; Michael D Hughson; Wendy E Hoy; Peter G Kerr; John F Bertram Journal: J Am Soc Nephrol Date: 2015-01-07 Impact factor: 10.121
Authors: Andrew D Patterson; Jessica A Bonzo; Fei Li; Kristopher W Krausz; Gabriel S Eichler; Sadaf Aslam; Xenia Tigno; John N Weinstein; Barbara C Hansen; Jeffrey R Idle; Frank J Gonzalez Journal: J Biol Chem Date: 2011-04-12 Impact factor: 5.157