Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats |
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| Authors: | Subramanyam N. Murthy Edward A. Pankey Ajaz A. Banka Adeleke M. Badejo Ryan Wekerle Vaitaitis Vilija Reza Izadpanah Philip J. Kadowitz Vivian A. Fonseca |
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| Affiliation: | 1. Neurodegeneration and Repair Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia;2. Oncology Research Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia;3. Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences, The University of New South Wales, Sydney NSW 2052, Australia;4. Bioanalytical Mass Spectrometry Facility, Bioanalytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia;1. Department of Biochemistry, Faculty of Medicine/Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, 34668 Haydarpasa, Istanbul, Turkey;2. TUBITAK Marmara Research Center, Genetic Engineering and Biotechnology Institute, P.O. Box 21, 41470 Gebze Kocaeli, Turkey |
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| Abstract: | ObjectiveWe compared the effect of the long acting basal insulin analog detemir with neutral protamine Hagedorn (NPH) insulin, and normal saline on recovery from vascular injury (balloon catheter mediated) in an animal model of insulin resistance.MethodsFemale Zucker fatty rats were administered NPH/detemir/saline for 7 days following which, they underwent balloon catheter mediated injury of left carotid artery, and were continued on the respective regimen for an additional 21 days when they were sacrificed. We evaluated the injured carotid artery for intimal hyperplasia (Intima/Media ratio) and also, aortic arch protein for markers of oxidative stress and inflammation, in addition to expression and phosphorylation of eNOS using well established methods.ResultsThere was a significant difference in intimal hyperplasia (Intima/Media ratio) between control and detemir treated rats (1.3 ± 0.09, 0.82 ± 0.08; p < 0.001) whereas the IM ratio in NPH treated rats was not significantly different from saline (1.17 ± 0.1). Expression of p-eNOS (ser-1177) in both NPH and insulin detemir (1.3 ± 0.15, 1.11 ± 0.12) was significantly higher than controls (0.56 ± 0.13; p < 0.05). We did not find significant differences in the expression of MnSOD, eNOS and NFκB-p65.ConclusionWe conclude that in insulin resistant states, treatment with Insulin detemir but not NPH is associated with less intimal hyperplasia, although both insulins increased eNOS phosphorylation. |
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