Thickening of basement membrane of muscle capillary in spontaneously diabetic KK mice.

Itabashi, Hiroshi; Ohneda, Akira; Iimura, Yasuo

doi:10.1620/tjem.133.339

Cited by 4 publications

(2 citation statements)

References 16 publications

(17 reference statements)

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“…In the past three decades, electron microscopy techniques have been applied in numerous animal models in an effort to compare CBMT changes in diabetics relative to age‐matched controls. The animal models are legion and include mice (Itabashi et al, 1981; Cuthbertson and Mandel, 1987; Diani et al, 1987; Carlson et al, 1997), rats (Fischer et al, 1981; Altshuler and Ornoy, 1986; Chakrabarti and Sima, 1987, 1989a, b; Robison et al, 1988; Copeland et al, 1990; Miyamura et al, 1999), dogs (Bloodworth et al, 1969; Engerman and Colquhoun, 1982; Stitt et al, 1994), and monkeys (Marion and Carlson, 1989). In addition, ultrastructural comparisons of BMs in a variety of tissues from diabetic and normal human subjects have been carried out (Danowski et al, 1972; Kilo et al, 1972; Dunn et al, 1979; Fischer et al, 1979; Jackson et al, 1982; Johnson et al, 1982; Raskin et al, 1983; Sosenko et al, 1984; Feingold et al, 1986, 1989; Osterby, 1990; Osterby et al, 1998, 2001; Bangstad et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice

et al. 2003

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Capillary basement membrane (CBM) thickening is an ultrastructural hallmark in diabetic patients and in animal models of diabetes. However, the wide variety of tissues sampled and diverse methods employed have made the interpretation of thickness data difficult. We showed previously that acellular glomerular BMs in OVE26 transgenic diabetic mice were thickened beyond normal age-related thickening, and in the current study we hypothesized that other microvascular BMs likewise would show increased widths relative to age-matched controls. Accordingly, a series of tissues, including skeletal and cardiac muscle, ocular retina and choriod, peripheral nerve, lung, pancreas, and renal glomerulus was collected from 300 -350-day-old normal and transgenic mice. Transmission electron micrographs of cross sections through capillary walls were prepared, and CBM thickness (CBMT) was determined by the "orthogonal intercept" method. Morphometric analyses showed highly variable transgene-related BMT increases in the sampled tissues, with glomerular BM showing by far the greatest increase (ϩ87%). Significant thickness increases were also seen in the retina, pulmonary alveolus, and thoracoabdominal diaphragm. BMT increases were not universal; however, most were modestly widened, and those that were thickest in controls generally showed the greatest increase. Although the pathogenesis of diabetes-related increases in CBM is poorly understood, data in the current study showed that in OVE26 transgenic mice increased BMT was a frequent concomitant of hyperglycemia. Accordingly, it seems likely that hyperglycemia-induced microvascular damage may be a contributing factor in diabetic BM disease, and that microvessel cellular and extracellular heterogeneity may limit the extent of CBM thickening in diverse tissues. Anat Rec Part A 271A: 332-341, 2003. © 2003 Key words: diabetes; basement membrane thickness; electron microscopy; transgenic diabetic mice OVE26 transgenic mice are diabetic as a result of the specific overexpression of calmodulin in pancreatic beta cells (Epstein et al., 1989(Epstein et al., , 1992. Histological studies show that this results in beta cell destruction early in life, and by 30 -55 days of age glucose values exceed 450 mg/dl. At the same time, insulin levels are reduced to 42% of control levels. OVE26 mice are a particularly valuable model of diabetes, because beta cell toxins need not be administered to induce the disease, and the animals can survive well over a year without exogenous insulin administration (probably because of a small amount of residual insulin secretion). Moreover, because both males and females are fertile for several months without insulin therapy, the transgenic line has been maintained continuously for more than 14 years.Several studies have shown that the OVE26 diabetic model is useful for examining chronic complications of diabetes. This was particularly evident in a previous study of the kidney (Carlson et al., 1997) in which transmission electron microscopy (TEM) morphometry sh...

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Section: Discussionmentioning

confidence: 99%

Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice

et al. 2003

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“…Studies in humans have demon strated increased CBMT in patients with diabetes mellitus of long duration [8][9][10][33][34][35][36][37], Diabetic animal model studies have reported similar observations. They included spontaneously diabetic mouse [38,39], hamster [40], alloxan-induced diabetic dog [41] and streptozotocininduced diabetic rhesus monkey [42]. All of these studies in animals affected with diabetes for at least 14 months have shown significant membrane thickening, indicating the apparent importance of the duration in addition to the severity of the disease.…”

Section: Discussionmentioning

confidence: 99%

Chronic Hyperglycemia in Experimental Diabetes mellitus of Short Duration Does Not Contribute to Muscle Capillary Basement Membrane Thickening

Copeland

Yatscoff²,

Mehta³

et al. 1990

Cells Tissues Organs

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The effect of chronic hyperglycemia on the relationship of nonenzymatic glycation and capillary basement membrane thickness in muscle was studied in streptozotocin-induced diabetic rats early in the course of diabetes mellitus. Diabetic animals were placed on either standard (24%) or restricted (8%) protein diet. The animals on 8% protein diet had elevated glycated hemoglobin levels (p < 0.01) and increased levels of nonenzymatic glycation of basement membrane (p < o.01) as compared to insulin-treated diabetic (euglycemic), age-matched control, and streptozotocin-injected nondia-betic animals also on 8% protein diet. In contrast, diabetic animals on restricted (8%) protein diet and those on standard (24%) protein diet showed no statistical differences between them with regards to the above parameters. Moreover, there were no statistical differences among diabetic and control animals on either 8 or 24% protein diet with respect to muscle capillary membrane thickness. Even though the peripheral muscle biopsy study of capillary basement membrane is less invasive than kidney biopsy, the results of this study suggest that neither nonenzymatic glycation nor basement membrane thickness can be utilized as predictors of renal dysfunction during early onset of diabetes mellitus.

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Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance

Brandt

Landmesser

Vogt³

et al. 1996

Diabetologia

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A differing individual expression of fructosyllysine-specific receptors has been found on the monocytes of 90 insulin-dependent diabetic patients and 101 healthy control subjects. The degree of receptor expression is neither age- nor sex-dependent; however, in the diabetic group it correlates significantly with the severity and age of onset of diabetic microangiopathy. To interpret the results of the human study, spontaneously diabetic and non-diabetic BB/OK rats were used to estimate tissue content of glucose-modified proteins and capillary basement membrane thickness in relation to the receptor expression on macrophages. In non-diabetic and diabetic rats no correlation was found between receptor expression and tissue content (i.e. artery, nerve) of fructosyllsine and fluorescent advanced glycation end products. However, animals which express the fructosyllysine receptor showed a greater increase in muscle capillary basement membrane thickness. There are indications that fructosyllysine receptor expression is positively associated with indices of diabetic complications such as microangiopathy and/or capillary basement membrane thickening.

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Thickening of basement membrane of muscle capillary in spontaneously diabetic KK mice.

Cited by 4 publications

References 16 publications

Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice

Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice

Chronic Hyperglycemia in Experimental Diabetes mellitus of Short Duration Does Not Contribute to Muscle Capillary Basement Membrane Thickening

Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance

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