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

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 microns 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 (approximately 1.8 times and 1.2 times control animals, respectively), urinary excretion of endogenous albumin (approximately 9 times and 4 times) and IgG (approximately 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.

Influence of Experimental Diabetes on the Microcirculation of Injured Peripheral Nerve

“…Intact or increased blood flow of uninjured nerves in rats with varying durations of experimental diabetes has been consistently found in our laboratory (24,26), as well as in others (29,30). In the present work, near-normal blood flow correlated with preserved microvessel caliber and density in diabetic animals.…”

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

“…Vascular permeability was measured at 24 weeks after the induction of experimental diabetes using a double isotope method [26,27]. In brief, a permeation marker, 125 I-human serum albumin, was injected intravascularly and allowed to circulate for 15 min.…”

The effect of aldose reductase inhibitors on glomerular prostaglandin production and urinary albumin excretion in experimental diabetes mellitus

“…These include increased glomerular filtration rate (GFR) [1][2][3][4][5][6][7][8][9][10][11][12][13], increased urinary albumin excretion (UAE) [13][14][15][16][17], increased production of vasoactive prostaglandins (PGs) by renal glomeruli [10,[18][19][20], and increased glomerular sorbitol accumulation [21]. Although there are several plausible ways in which these changes could be related, the data linking these phenomena have been conflicting and confusing.…”