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  • 1
    ISSN: 1432-0428
    Keywords: Pericyte ; diabetes ; acellular capillaries ; skeletal muscle ; diabetic retinopathy ; capillary basement membrane width
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastractural morphometry was used to quantify capillary basement membrane width, pericyte coverage of capillaries, pericyte degeneration, and the extent of acellular capillaries in skeletal muscle obtained at autopsy from neck, thigh, calf and foot of five male and four female diabetic subjects and an equal number of sex- and age-matched nondiabetic subjects. Within diabetic or nondiabetic subjects, the trend for all four parameters to increase in frequency or magnitude in the order neck 〈 thigh 〈 calf was highly significant; the only statistically significant difference between calf and foot muscles for any of the four parameters was capillary basement membrane width for nondiabetic subjects, which was significantly thinner in foot than in calf muscle (t=2.45;p〈0.05). Pericyte coverage of capillaries did not differ between diabetic and nondiabetic subjects for each muscle examined; however, capillary basement membrane width, the frequency of pericyte debris and acellular capillaries were increased significantly in the lower extremity muscles of diabetic compared to nondiabetic subjects, and the magnitude of the difference between these two groups increased in the order thigh 〈 calf 〈 foot. The observations that pericyte degeneration and acellular capillaries are present in skeletal muscle as well as in retinal microvessels suggest that common pathophysiological mechanisms may contribute to vascular disease in these two very different tissues. The additional finding that relative differences between diabetic and nondiabetic subjects, in the frequency and magnitude of these changes, increase in the order neck 〈 calf 〈 foot is consistent with the marked increase in peripheral vascular disease and gangrene in the lower extremities of diabetic patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Nicotinamide ; streptozotocin ; albumin permeation ; glomerular filtration rate ; blood flow ; urinary protein excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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.
    Type of Medium: Electronic Resource
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