Apoptosis in the diabetic autonomic nervous system has been less completely studied than in the somatic nervous system. Nevertheless, important information on the regulation of apoptosis in the autonomic nervous system has become available in the last 5 years. In rat superior cervical ganglion (SCG) cultures, there is evidence of glucose-induced apoptosis in SCG neurons, although they are considerably less sensitive to glucose toxicity than DRG neurons treated with the same high glucose conditions (105). Apoptosis in SCG neurons is coupled with inhibition of neurite growth, reduction in neurite caliber, beading of neurites, and retraction of the neurite growth cone consistent with degeneration of autonomic fibers (105). In agreement with these findings, acute streptozotocin diabetes is associated with evidence of PCD in a small number of auto-nomic neurons and activation of the apoptotic cascade occurs relatively early in diabetic autonomic neuropathy (106). However, there is no significant neuron loss in chronic diabetes in either the rat superior mesenteric or superior cervical sympathetic ganglia, indicating that apoptotic neuronal cell death alone is unlikely to account for the severity of autonomic neuropathy observed in type 1 diabetes (107).
As with DRG neurons, insulin and IGF-I inhibit both the induction of apoptosis and loss of autonomic neurons (105,108). Furthermore, loss of autonomic neurons is more severe in animal models of type 1 in comparison with type 2 diabetes, suggesting a protective role for insulin and IGF-I and that failure of these protective systems may account for the severity of autonomic dysfunction in type 1 diabetes (106,109). In support of this concept, differences in neuroaxonal dystrophy have been observed in different animal models of autonomic neuropathy: two models of type 1 diabetes, the streptozotocin diabetic and BB/W rat develop marked hyperglycemia and concomitant deficiency in both circulating insulin and IGF-I. These type 1 animals develop neuroaxonal dystrophy in nerve terminals in the prevertebral sympathetic ganglia and the distal portions of noradrenergic ileal mesenteric nerves. In contrast, the Zucker diabetic fatty rat, an animal model of type 2 diabetes, despite developing severe hyperglycemia comparable with that in the STZ- and BB/W-diabetic rat models does not develop neuroaxonal dystrophy. Unlike the type 1 models of diabetes, the Zucker diabetic fatty rats have significant hyperinsulinemia and normal levels of plasma IGF-I (109).
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