Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysfunction of the autonomic nervous system is a recognized complication of diabetes. Neuroaxonal dystrophy (NAD), a distinctive axonopathy involving distal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in human and several insulinopenic experimental rodent models. Recent studies have suggested that loss of the neurotrophic effects of insulin and/or IGF-I on sympathetic neurons and not hyperglycemia per se, may underlie the development of sympathetic NAD. The streptozotocin (STZ)-diabetic and BB/W rat, the most commonly used experimental rodent models, develop marked hyperglycemia and concomitant deficiency in both circulating insulin and IGF-I. These animals reproducibly develop NAD in nerve terminals in the prevertebral sympathetic ganglia and the distal portions of noradrenergic ileal mesenteric nerves. The Zucker Diabetic Fatty (ZDF) rat, an animal model of type 2 diabetes, also develops severe hyperglycemia comparable to that in the STZ- and BB/W-diabetic rat models, although in the presence of hyperinsulinemia. In our study, ZDF rats maintained for 6 to 7 months in a severely diabetic state, as assessed by plasma glucose and glycated hemoglobin levels, maintained significant hyperinsulinemia and normal levels of plasma IGF-I at sacrifice. NAD did not develop in diabetic ZDF rat sympathetic ganglia and ileal mesenteric nerves as assessed by quantitative ultrastructural techniques, which is in dramatic contrast to neuropathologic findings in comparably hyperglycemic 6-month STZ-diabetic insulinopenic rats. These data combined with our previous results argue very strongly that hyperglycemia is not the critical and sufficient element in the pathogenesis of diabetes-induced NAD, rather that it is the loss of trophic support, most likely of IGF-I or insulin, that causes NAD.
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PMID:Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy. 1281 7

Dysfunction of the autonomic nervous system is a recognized complication of diabetes, ranging in severity from relatively minor sweating and pupillomotor abnormality to debilitating interference with cardiovascular, genitourinary, and alimentary dysfunction. Neuroaxonal dystrophy (NAD), a distinctive distal axonopathy involving terminal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in man and several insulinopenic experimental rodent models. Although the pathogenesis of diabetic sympathetic NAD is unknown, recent studies have suggested that loss of the neurotrophic effects of insulin and/or insulin-like growth factor-I (IGF-I) on sympathetic neurons rather than hyperglycemia per se, may be critical to its development. Therefore, in our current investigation we have compared the sympathetic neuropathology developing after 8 months of diabetes in the streptozotocin (STZ)-induced diabetic rat and BB/ Wor rat, both models of hypoinsulinemic type 1 diabetes, with the BBZDR/Wor rat, a hyperglycemic and hyperinsulinemic type 2 diabetes model. Both STZ- and BB/Wor-diabetic rats reproducibly developed NAD in nerve terminals in the prevertebral superior mesenteric sympathetic ganglia (SMG) and ileal mesenteric nerves. The BBZDR/Wor-diabetic rat, in comparison, failed to develop superior mesenteric ganglionic NAD in excess of that of age-matched controls. Similarly, NAD which developed in axons of ileal mesenteric nerves of BBZDR/Wor rats was substantially less frequent than in BB/Wor- and STZ-rats. These data, considered in the light of the results of previous experiments, argue that hyperglycemia alone is not sufficient to produce sympathetic ganglionic NAD, but rather that it may be the diabetes-induced superimposed loss of trophic support, likely of IGF-I, insulin, or C-peptide, that ultimately causes NAD.
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PMID:Experimental rat models of types 1 and 2 diabetes differ in sympathetic neuroaxonal dystrophy. 1519 24