Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats

G. Pugliese, Ronald Tilton, A. Speedy, K. Chang, E. Santarelli, M. A. Province, D. Eades, W. R. Sherman, J. R. Williamson

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Rats injected i. p. with a single dose of nicotinamide (250 mg/kg) 15 min prior to i.v. injection of streptozotocin (65 mg/kg) develop a very mild form of diabetes characterized by slight elevations of plasma glucose, increased levels of HbA1, and reduced insulin secretion in response to an i.v. glucose tolerance test. These rats gain weight normally and they are not hyperphagic, glycosuric, or polyuric. The effects of this very mild form of diabetes vs overt streptozotocin diabetes of three months duration on regional vascular 131I-albumin clearance, blood flow (assessed by 15 μm 85Sr-microspheres), and renal filtration function were examined in male Sprague-Dawley rats. Plasma glucose levels of rats with mild diabetes were 7.4±0.9 (mean±SD) (mmol/l) vs 6.5±0.6 for control rats and 31.3±6.0 for overtly diabetic rats. HbA1 levels were increased 1.4 fold in mildly diabetic and 2.3 fold in overtly diabetic rats. Vascular clearance of 131I-albumin was markedly increased in ocular tissues (anterior uvea, retina, and choroid), sciatic nerve, aorta, new (subcutaneous) granulation tissue, and kidney of both diabetic groups, although increases in overtly diabetic rats exceeded those in the mildly diabetic group (2.2-4.6 times control animals vs 1.6-3.3 times, respectively). Likewise, both overt and very mild diabetes markedly increased glomerular filtration rate (∼1.8 times and 1.2 times control animals, respectively), urinary excretion of endogenous albumin (∼9 times and 4 times) and IgG (∼15 times and 4 times), as well as regional blood flow in the anterior uvea, choroid, and sciatic nerve. Increases in tissue sorbitol levels were much larger in overtly diabetic rats (generally 10-20 times control animals) than in mildly diabetic rats (1.5-3 times controls). myo-Inositol levels were significantly decreased only in lens and sciatic nerve of overtly diabetic rats. These observations indicate that even very mild diabetes is associated with vascular functional changes which develop more slowly than in overtly diabetic rats, but are disproportionately large (in view of the minimal increases in glycaemia and tissue polyol levels) compared to those in overtly diabetic rats.

Original languageEnglish (US)
Pages (from-to)845-857
Number of pages13
JournalDiabetologia
Volume32
Issue number12
DOIs
StatePublished - Dec 1989
Externally publishedYes

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Blood Vessels
Hemodynamics
Sciatic Nerve
Uvea
Albumins
Choroid
Glycosylated Hemoglobin A
Kidney
Glucose
Niacinamide
Experimental Diabetes Mellitus
Granulation Tissue
Sorbitol
Subcutaneous Tissue
Regional Blood Flow
Inositol
Glucose Tolerance Test
Streptozocin
Glomerular Filtration Rate
Microspheres

Keywords

  • albumin permeation
  • blood flow
  • glomerular filtration rate
  • Nicotinamide
  • streptozotocin
  • urinary protein excretion

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Pugliese, G., Tilton, R., Speedy, A., Chang, K., Santarelli, E., Province, M. A., ... Williamson, J. R. (1989). Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats. Diabetologia, 32(12), 845-857. https://doi.org/10.1007/BF00297449

Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats. / Pugliese, G.; Tilton, Ronald; Speedy, A.; Chang, K.; Santarelli, E.; Province, M. A.; Eades, D.; Sherman, W. R.; Williamson, J. R.

In: Diabetologia, Vol. 32, No. 12, 12.1989, p. 845-857.

Research output: Contribution to journalArticle

Pugliese, G, Tilton, R, Speedy, A, Chang, K, Santarelli, E, Province, MA, Eades, D, Sherman, WR & Williamson, JR 1989, 'Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats', Diabetologia, vol. 32, no. 12, pp. 845-857. https://doi.org/10.1007/BF00297449
Pugliese G, Tilton R, Speedy A, Chang K, Santarelli E, Province MA et al. Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats. Diabetologia. 1989 Dec;32(12):845-857. https://doi.org/10.1007/BF00297449
Pugliese, G. ; Tilton, Ronald ; Speedy, A. ; Chang, K. ; Santarelli, E. ; Province, M. A. ; Eades, D. ; Sherman, W. R. ; Williamson, J. R. / Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats. In: Diabetologia. 1989 ; Vol. 32, No. 12. pp. 845-857.
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