ACTH4-9 analogue ORG 2766 can improve existing neuropathy in streptozocin-induced diabetic rats.
The effect of treatment of an existing neuropathy in streptozocin-induced diabetic rats with the ACTH4-9 analogue ORG 2766 was examined. Four groups of rats were studied: group 1 consisted of age-matched, non-diabetic controls and groups 2, 3 and 4 of diabetic rats. Sensory and motor nerve conduction velocity (SNCV and MNCV) were measured at weeks 0, 4, 6, 8 and 10. Four weeks after the administration of streptozocin (STZ) all diabetic rats showed a significant slowing of SNCV and MNCV. Treatment was then started: group 2 was treated with placebo, group 3 with a low dos (1 microgram) of ACTH4-9 subcutaneously every 48 h, and group 4 with a high dos (10 micrograms) of ACTH4-9 subcutaneously every 48 h. The animals treated with the high peptide dosage showed a significant improvement in both SNCV and MNCV from week 6 onwards, whereas this beneficial effect was not demonstrated for the rats treated with the low dosage. This study demonstrates that the ACTH4-9 analogue ORG 2766 can ameliorate existing diabetic neuropathy in STZ-induced diabetic rats.
Bravenboer
B
B
Department of Internal Medicine, Rudolf Magnus Institute, University of Utrecht, The Netherlands.
Kappelle
A C
AC
van Buren
T
T
Erkelens
D W
DW
Gispen
W H
WH
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013979:Tibial Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013997:Time Factors
D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone