Effect of Streptozotocin-Induced Diabetes on Kidney Weight and Compensatory Hypertrophy in the Rat

Ross, Jeffery S.; Goldman, Jack K.

doi:10.1210/endo-88-4-1079

Cited by 53 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This discrepancy could be due to the shorter duration of diabetes in the rat. On the other hand there are striking similarities, such as increase in kidney size [22,27,29], in glomerular volume [9,27,38], in glomerular basement membrane thickness [4,12,28,36], increase of mesanglum [10,14,19] and basement membrane-like material [1,35,37].…”

Section: Discussionmentioning

confidence: 99%

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Rasch

1979

Diabetologia

View full text Add to dashboard Cite

Smmnm'y.A quantitative morphological study of the mesangial regions has been performed on the kidneys of two groups of insulin treated diabetic rats 6 months after the induction of diabetes. In one group reasonably good control of plasma glucose levels (182 + 20 (SD) rag/100 ml at 0800 h; 95 + 35 mg/ 100 ml at 2300 h) was achieved. This group showed no mesangial changes when compared to a nondiabetic control group. In the second diabetic group poor control was intended (plasma glucose 452 +_ 41mg/100ml and 555 _+ 86mg/100ml respectively). The following differences were noted when this group was compared to the non-diabetic controls and to the rats in which the blood glucose was wellcontrolled: 1. Increase in total mesangial volume per glomerulus by 42% and 38% (2p = 0.025 and 0.037); 2. Increase in the total amount of basement membrane-like material (BMLM) per glomerulus by 30 and 27% (2p = 0.030 and 0.046); 3. Increase in the total mesangial cell volume per glomerulus by 46 and 43% (2p = 0.033 and 0.048); 4. Increase in volume of electron dense material in the BMLM by about 200% compared to both groups (2p ---0.001 and 0.0003). The study has shown that the mesangial regions also are involved in the diabetic glomerulopathy of experimental diabetes. The morphological changes including increased amounts of basement membrane material are prevented by proper glycaemic control.Key words: Mesangial region, streptozotocin diabetes, glucose control in rats, diabetic glomerulopathy, stereology, insulin treatment.It has previously been shown that kidneys and glomeruli become enlarged over a 6 months period in rats with constant high plasma glucose levels [27].Glomerular basement membranes (GBM) were also significantly thicker than in non-diabetic control rats [28]. There is also evidence of mesangial changes in experimental diabetes in the rat [11,13,19,34,35], similar to those found in humans [21,23,24,35]. The mesangial changes due to experimental diabetes are described as an increase of the mesangium, with increased amounts of basement membrane-like material (BMLM). The mesangial regions also become strongly reactive to periodic acid-Schiff (PAS) and with the immunofluorescent technique a positive reaction to immunoglobulin and complement is seen.Consequently, the experimental diabetic rat was considered an acceptable model for studying the prevention of diabetic mesangial changes using morphometric techniques. The cationic stain Alcian Blue [31], which reveals the surface coat of the glomerular cells [2], is also bound to the mesangial regions of diabetic and non-diabetic rats [25] and this electron microscopic histochemical technique was also used in the present study. Material and MethodDetailed description of the animals, their treatment and the tissue sampling procedure has been given previously [27,28]. In summary, streptozotocin diabetes was induced by administrating 90 mg/kg intravenously. Three groups of female Wistar rats were used. In one group of 8 streptozotocin diabetic rats good diabetic control was plan...

show abstract

Section: Discussionmentioning

confidence: 99%

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Rasch

1979

Diabetologia

View full text Add to dashboard Cite

show abstract

“…Experimental and clinical diabetes is characterized by increased perfusion and an increased glomerular filtration rate (GFR) as well as renal hypertrophy occurring early in the course of DN [1,2,3,4]. One of the mediators implicated in the development of DN is nitric oxide (NO) [5].…”

Section: Introductionmentioning

confidence: 99%

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Khamaisi¹,

Keynan²,

Bursztyn³

et al. 2006

Nephron Physiol

View full text Add to dashboard Cite

Background: Several studies have suggested that an early increase in renal nitric oxide (NO) production or activity mediates pathophysiologic and morphologic changes in diabetic nephropathy. To evaluate the role of NO in developing diabetic kidney disease, we studied the NO system in streptozotocin (STZ)-induced diabetic rats for a period of 8 weeks. Methods: Control rats, STZ-induced diabetic rats, and STZ-induced diabetic rats treated with insulin were monitored and sacrificed at 1, 2, and 8 weeks. Urinary cGMP was measured, and the levels and activity of NO synthase (NOS) isoforms in the kidney cortex were determined at specific times by immunoblotting and diaphorase staining. Results: Diabetic rats had increased kidney weight, urinary volume, glucose, sodium and potassium excretion, which was precluded by insulin treatment. Creatinine clearance was increased in the diabetic group and reversed by insulin treatment. Urinary cGMP decreased by 71, 93, and 92% at 1, 2, and 8 weeks of diabetes, respectively, compared with the control animals. Insulin treatment curtailed the urinary cGMP reduction in diabetic animals. Total NOS activity in the renal cortex was reduced by 65, 52, and 44% after 1, 2, and 8 weeks of diabetes, respectively, and returned to normal levels upon insulin treatment. NADPH diaphorase staining of renal cortical slices showed a 77, 63, and 70% decrease in neuronal NOS isoform activity in the macula densa after 1, 2, and 8 weeks of diabetes, respectively, compared with control non-diabetic animals. This reduction was normalized by insulin treatment. Endothelial NOS protein expression in the kidney cortex tended to increase after 1 week of diabetes and its level was elevated significantly after 2 and 8 weeks of diabetes. However, neuronal NOS protein expression in the kidney cortex was reduced by 52% in 2-week diabetic animals, but this reduction was normalized by insulin treatment. Conclusions: The decreased renal NOS activity during the late phase of diabetes is partially associated with a decrease in neuronal NOS activity and protein expression in kidney macula densa.

show abstract

“…These findings raise the possibility that polyamines produced in the distal nephron may mediate the early diabetic kidney growth of the proximal tubules via a paracrine mechanism. Diabetes 52: 1235-1239, 2003 I n the very early phases of human and experimental diabetes, the kidney becomes large, mainly due to growth of the proximal tubule (1)(2)(3). Because renal enlargement and accompanying glomerular hyperfiltration contribute to the later development of overt diabetic kidney disease (4), it is worthwhile to understand what causes the kidney to grow in diabetes.…”

mentioning

confidence: 99%

Increased Expression of Ornithine Decarboxylase in Distal Tubules of Early Diabetic Rat Kidneys

et al. 2003

View full text Add to dashboard Cite

Polyamines are small biogenic molecules that are essential for cell cycle entry and progression and proliferation. They can also contribute to hypertrophy. The activity of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis, increases in the early diabetic kidney to enable renal hypertrophy. Inhibition of ODC in early diabetes attenuates diabetic renal hypertrophy and glomerular hyperfiltration. The current studies examine the temporal profile of renal ODC protein expression and localization, intrarenal polyamine levels, and sites of proliferation in kidneys of rats during the first 7 days of streptozotocin diabetes. ODC mRNA and protein content were increased in diabetic kidneys. High-performance liquid chromatography analysis showed increased intrarenal polyamine concentrations peaking after 24 h of diabetes. A subsequent increase in the number of proliferating proximal tubular cells was detected by in vivo 5-bromodeoxyuridine (BrdU) incorporation on day 3. Surprisingly, immunohistochemical studies revealed that increased ODC protein was apparent only in distal nephrons, whereas the main site of diabetic kidney hypertrophy is the proximal tubule. These findings raise the possibility that polyamines produced in the distal nephron may mediate the early diabetic kidney growth of the proximal tubules via a paracrine mechanism.

show abstract

Effect of Streptozotocin-Induced Diabetes on Kidney Weight and Compensatory Hypertrophy in the Rat

Cited by 53 publications

References 0 publications

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Role of Renal Nitric Oxide Synthase in Diabetic Kidney Disease during the Chronic Phase of Diabetes

Increased Expression of Ornithine Decarboxylase in Distal Tubules of Early Diabetic Rat Kidneys

Contact Info

Product

Resources

About