Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Apr;83(4):1384–1389. doi: 10.1172/JCI114026

Control of glomerular hypertension by insulin administration in diabetic rats.

J W Scholey 1, T W Meyer 1
PMCID: PMC303832  PMID: 2649514

Abstract

Micropuncture studies were performed in Munich Wistar rats made diabetic with streptozotocin and in normal control rats. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (approximately 300 mg/dl). Group 1 diabetic rats studied after routine micropuncture preparation exhibited elevation of the single nephron glomerular filtration rate (SNGFR) due to increases in the glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 diabetic rats infusion of insulin to achieve acute blood glucose control normalized the glomerular transcapillary pressure gradient while increasing the glomerular ultrafiltration coefficient, so that SNGFR remained elevated. Persistent elevation of SNGFR despite normalization of the transcapillary pressure gradient was also observed in group 3 diabetic rats infused with insulin plus sufficient dextrose to maintain hyperglycemia. These studies indicate that glomerular capillary hypertension in diabetes is an acutely reversible consequence of insulin deficiency and not the result of renal hypertrophy.

Full text

PDF
1389

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bank N., Klose R., Aynedjian H. S., Nguyen D., Sablay L. B. Evidence against increased glomerular pressure initiating diabetic nephropathy. Kidney Int. 1987 Apr;31(4):898–905. doi: 10.1038/ki.1987.83. [DOI] [PubMed] [Google Scholar]
  2. Baylis C. Glomerular ultrafiltration in the pseudopregnant rat. Am J Physiol. 1982 Sep;243(3):F300–F305. doi: 10.1152/ajprenal.1982.243.3.F300. [DOI] [PubMed] [Google Scholar]
  3. Blantz R. C., Konnen K. S., Tucker B. J. Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat. J Clin Invest. 1976 Feb;57(2):419–434. doi: 10.1172/JCI108293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blantz R. C., Tucker B. J., Gushwa L., Peterson O. W. Mechanism of diuresis following acute modest hyperglycemia in the rat. Am J Physiol. 1983 Feb;244(2):F185–F194. doi: 10.1152/ajprenal.1983.244.2.F185. [DOI] [PubMed] [Google Scholar]
  5. Christiansen J. S., Feldt-Rasmussen B., Parving H. H. Short-term inhibition of prostaglandin synthesis has no effect on the elevated glomerular filtration rate of early insulin-dependent diabetes. Diabet Med. 1985 Jan;2(1):17–20. doi: 10.1111/j.1464-5491.1985.tb00586.x. [DOI] [PubMed] [Google Scholar]
  6. Christiansen J. S., Frandsen M., Parving H. H. The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus. Diabetologia. 1981 Mar;20(3):199–204. doi: 10.1007/BF00252628. [DOI] [PubMed] [Google Scholar]
  7. Deen W. M., Maddox D. A., Robertson C. R., Brenner B. M. Dynamics of glomerular ultrafiltration in the rat. VII. Response to reduced renal mass. Am J Physiol. 1974 Sep;227(3):556–562. doi: 10.1152/ajplegacy.1974.227.3.556. [DOI] [PubMed] [Google Scholar]
  8. Deen W. M., Troy J. L., Robertson C. R., Brenner B. M. Dynamics of glomerular ultrafiltration in the rat. IV. Determination of the ultrafiltration coefficient. J Clin Invest. 1973 Jun;52(6):1500–1508. doi: 10.1172/JCI107324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dilley J. R., Corradi A., Arendshorst W. J. Glomerular ultrafiltration dynamics during increased renal venous pressure. Am J Physiol. 1983 Jun;244(6):F650–F658. doi: 10.1152/ajprenal.1983.244.6.F650. [DOI] [PubMed] [Google Scholar]
  10. Dworkin L. D., Hostetter T. H., Rennke H. G., Brenner B. M. Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. J Clin Invest. 1984 May;73(5):1448–1461. doi: 10.1172/JCI111349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Esmatjes E., Fernandez M. R., Halperin I., Camps J., Gaya J., Arroyo V., Rivera F., Figuerola D. Renal hemodynamic abnormalities in patients with short term insulin-dependent diabetes mellitus: role of renal prostaglandins. J Clin Endocrinol Metab. 1985 Jun;60(6):1231–1236. doi: 10.1210/jcem-60-6-1231. [DOI] [PubMed] [Google Scholar]
  12. Finn W. F. Compensatory renal hypertrophy in Sprague-Dawley rats: glomerular ultrafiltration dynamics. Ren Physiol. 1982;5(5):222–234. doi: 10.1159/000172861. [DOI] [PubMed] [Google Scholar]
  13. Hirose K., Osterby R., Nozawa M., Gundersen H. J. Development of glomerular lesions in experimental long-term diabetes in the rat. Kidney Int. 1982 May;21(5):689–695. doi: 10.1038/ki.1982.82. [DOI] [PubMed] [Google Scholar]
  14. Hirose K., Tsuchida H., Osterby R., Gundersen H. J. A strong correlation between glomerular filtration rate and filtration surface in diabetic kidney hyperfunction. Lab Invest. 1980 Nov;43(5):434–437. [PubMed] [Google Scholar]
  15. Hostetter T. H., Rennke H. G., Brenner B. M. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982 Mar;72(3):375–380. doi: 10.1016/0002-9343(82)90490-9. [DOI] [PubMed] [Google Scholar]
  16. Hostetter T. H., Troy J. L., Brenner B. M. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981 Mar;19(3):410–415. doi: 10.1038/ki.1981.33. [DOI] [PubMed] [Google Scholar]
  17. Ichikawa I., Maddox D. A., Brenner B. M. Maturational development of glomerular ultrafiltration in the rat. Am J Physiol. 1979 May;236(5):F465–F471. doi: 10.1152/ajprenal.1979.236.5.F465. [DOI] [PubMed] [Google Scholar]
  18. Ichikawa I., Miele J. F., Brenner B. M. Reversal of renal cortical actions of angiotensin II by verapamil and manganese. Kidney Int. 1979 Aug;16(2):137–147. doi: 10.1038/ki.1979.115. [DOI] [PubMed] [Google Scholar]
  19. Ichikawa I., Purkerson M. L., Klahr S., Troy J. L., Martinez-Maldonado M., Brenner B. M. Mechanism of reduced glomerular filtration rate in chronic malnutrition. J Clin Invest. 1980 May;65(5):982–988. doi: 10.1172/JCI109784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jensen P. K., Christiansen J. S., Steven K., Parving H. H. Strict metabolic control and renal function in the streptozotocin diabetic rat. Kidney Int. 1987 Jan;31(1):47–51. doi: 10.1038/ki.1987.7. [DOI] [PubMed] [Google Scholar]
  21. Jensen P. K., Steven K., Blaehr H., Christiansen J. S., Parving H. H. Effects of indomethacin on glomerular hemodynamics in experimental diabetes. Kidney Int. 1986 Feb;29(2):490–495. doi: 10.1038/ki.1986.26. [DOI] [PubMed] [Google Scholar]
  22. Kurokawa K., Silverblatt F. J., Klein K. L., Wang M. S., Lerner R. L. Binding of 125I-insulin to the isolated glomeruli of rat kidney. J Clin Invest. 1979 Nov;64(5):1357–1364. doi: 10.1172/JCI109592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Michels L. D., Davidman M., Keane W. F. Determinants of glomerular filtration and plasma flow in experimental diabetic rats. J Lab Clin Med. 1981 Dec;98(6):869–885. [PubMed] [Google Scholar]
  24. Osterby R., Gundersen H. J. Glomerular size and structure in diabetes mellitus. I. Early abnormalities. Diabetologia. 1975 Jun;11(3):225–229. doi: 10.1007/BF00422326. [DOI] [PubMed] [Google Scholar]
  25. Rasch R. Control of blood glucose levels in the streptozotocin diabetic rat using a long-acting heat-treated insulin. Diabetologia. 1979 Mar;16(3):185–190. doi: 10.1007/BF01219796. [DOI] [PubMed] [Google Scholar]
  26. Schambelan M., Blake S., Sraer J., Bens M., Nivez M. P., Wahbe F. Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus. J Clin Invest. 1985 Feb;75(2):404–412. doi: 10.1172/JCI111714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tucker B. J., Blantz R. C. Factors determining superficial nephron filtration in the mature, growing rat. Am J Physiol. 1977 Feb;232(2):F97–104. doi: 10.1152/ajprenal.1977.232.2.F97. [DOI] [PubMed] [Google Scholar]
  28. Woods L. L., Mizelle H. L., Hall J. E. Control of renal hemodynamics in hyperglycemia: possible role of tubuloglomerular feedback. Am J Physiol. 1987 Jan;252(1 Pt 2):F65–F73. doi: 10.1152/ajprenal.1987.252.1.F65. [DOI] [PubMed] [Google Scholar]
  29. Zatz R., Dunn B. R., Meyer T. W., Anderson S., Rennke H. G., Brenner B. M. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986 Jun;77(6):1925–1930. doi: 10.1172/JCI112521. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES