caa a22 4500 475770862 CHVBK 20180406123616.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s001250050014 doi (NATIONALLICENCE)springer-10.1007/s001250050014 Functional and structural abnormalities in the nerves of Type I diabetic baboons: aminoguanidine treatment does not improve nerve function [Elektronische Daten] [A. M. Birrell, S. J. Heffernan, A. D. Ansselin, S. McLennan, D. K. Church, AG Gillin, D. K. Yue] Aims/hypothesis. To improve understanding of the pathophysiology of diabetic neuropathy and to establish a primate model for experimental studies, we examined nerve changes in baboons with Type I (insulin-dependent) diabetes mellitus. We also examined the effect of aminoguanidine (an inhibitor of the formation of advanced glycation end products) on nerve function.¶Methods. Male baboons (Papio hamadryas) were assigned to four groups; control, diabetic, control and diabetic treated with aminoguanidine. Diabetes was induced with streptozotocin (60 mg/kg, intravenous). Insulin and aminoguanidine (10 mg/kg) were injected subcutaneously daily. Motor and sensory nerve conduction velocity was measured using standard techniques. Autonomic function was examined by measuring heart rate response to positional change. Sural nerve morphometry was analysed in the diabetic group (mean duration 5.5 years) along with their age-matched controls.¶Results. The diabetic groups were smaller in size with a mean HbA1 c of 8.9 ± 1.2 %. The nerve conduction velocity and heart rate response was reduced in the diabetic groups. Morphometric analysis of the diabetic sural nerve showed smaller axon diameter (2.99 ± 0.06 μm vs 3.29 ± 0.06 μm; p < 0.01) accompanied by thinner myelin (1.02 ± 0.02 μm vs 1.15 ± 0.02 μm, p < 0.01) with no change in the axon density. Treatment with aminoguanidine for 3 years had no effect on glycaemic control and did not restore conduction velocity or autonomic dysfunction in the diabetic animals, contrary to the studies in rats.¶Conclusions/interpretation. These results show that the primate is a good model to study diabetic neuropathy and suggest that the accumulation of advanced glycation end products are not an early mechanism of nerve damage in this disorder. [Diabetologia (2000) 43: 110-116] Springer-Verlag Berlin Heidelberg, 2000 Keywords Diabetic complications, neuropathy, autonomic, nerve conduction velocity, aminoguanidine, monkey, morphometry, myelin, advanced glycation end products nationallicence Birrell A. M. The Departments of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia, AU aut Heffernan S. J. The Departments of Endocrinology, The University of Sydney, Australia, AU aut Ansselin A. D. The Electron Microscopy Unit, The University of Sydney, Australia, AU aut McLennan S. The Departments of Endocrinology, The University of Sydney, Australia, AU aut Church D. K. The Department of Veterinary Clinical Science, The University of Sydney, Australia, AU aut Gillin AG The Departments of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia, AU aut Yue D. K. The Departments of Endocrinology, The University of Sydney, Australia, AU aut https://doi.org/10.1007/s001250050014 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050014 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Birrell A. M. The Departments of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia, AU aut NATIONALLICENCE 700 1- Heffernan S. J. The Departments of Endocrinology, The University of Sydney, Australia, AU aut NATIONALLICENCE 700 1- Ansselin A. D. The Electron Microscopy Unit, The University of Sydney, Australia, AU aut NATIONALLICENCE 700 1- McLennan S. The Departments of Endocrinology, The University of Sydney, Australia, AU aut NATIONALLICENCE 700 1- Church D. K. The Department of Veterinary Clinical Science, The University of Sydney, Australia, AU aut NATIONALLICENCE 700 1- Gillin AG The Departments of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia, AU aut NATIONALLICENCE 700 1- Yue D. K. The Departments of Endocrinology, The University of Sydney, Australia, AU aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer