Diabetes mellitus tends to cause more severe microvascular complications in juvenile than adult animals and man. This situation may exist in part because the diabetic process in juvenile animals inhibits the development of new, nutritive microvessels during growth as well as impairing growth of existing vessels. To evaluate this hypothesis, the growth characteristics of the juvenile vasculature in the small intestine and cerebral cortex will be determined in terms of enlargement of existing vessels as well as development of new, functional microvessels. Very little information is available on the growth characteristics of the microvasculature within organs during juvenile life for normal or diabetic animals. Pilot studies in the current grant period indicate that the development of new microvessels in juvenile life primarily occurs at the level of the smallest vessels which also corresponds to the vascular section with the greatest decrease in vessels during juvenile diabetes. In addition, studies in progress indicate that vascular smooth cells around microvessels in normal juvenile rats increase in length and width during normal growth. The proposed studies will consider the possibility that the microvasculature of the juvenile animal is more sensitive to deleterious effects of hyperglycemia than the adult animal because of the growth phase of the vasculature. During the current grant period, I demonstrated that exposure of intestinal microvasculature of normoglycemic adult rats to intraperitoneal hyperglycemia would cause pathological changes qualitatively, temporally and in many cases, quantitatively similar to those of diabetic rats. In effect, an intra-abdominal glucose concentration of 300 mg percent or less during twice daily two hour exposures, was an adequate threshold to initiate diabetic-like microangiopathy in an otherwise healthy animal. By using the intraperitoneal hyperglycemia method, it may be possible to demonstrate the minimum thresholds of glucose concentration and duration of exposure required to cause microvascular pathology. Furthermore, the approach may indicate the juvenile animal has lower thresholds and therefore greater sensitivity to microvascular damage than adult animals. This information on both juvenile and adult animals may prove to be very useful in establishing diabetic treatment protocols which avoid the severity of hyperglycemia at which microangiopathy begins to occur.
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