Abstract
Previous evidence supports the view that insulin, as well as insulin like growth factor-1 (IGF-1) provides neurotropic support for neurons in the central nervous system (CNS) and peripheral nervous system (PNS). In the present study we evaluated the effects of the intravenous infusion of IGF-1 on both necrosis and apoptosis in the CNS of streptozotocin induced diabetic animals before and/or following middle cerebral artery occlusion (MCAO) with reperfusion. The lesion volume was used as an index of necrosis and the sensorimotor cortex (layers 5 and 6) as well as the CA1 and CA3 regions of the hippocampus were analyzed for apoptosis using TUNEL staining and Caspase-3 immunoreactivity. A large lesion volume was produced in diabetic animals after 2-h MCAO and 24-h reperfusion. Diabetic animals also had an elevated basal level of apoptotic cells that are bilaterally distributed. Apoptosis was further increased over basal after 2-h MCAO and 24-h reperfusion. The acute administration of IGF-1 30-min before or 2 h after MCAO followed by 24-h reperfusion decreased the lesion volume as well as the number of apoptotic cells in the cortical penumbra. Apoptosis as assessed by TUNEL and caspase-3 immunoreactivity was decreased in select sensorimotor cortex and hippocampal areas.
We conclude that treatment with IGF-1 before or after ischemic insult significantly decreases both lesion volume and apoptosis in selected areas of the cortex and hippocampus.
Similar content being viewed by others
References
W.H. Lee, J.A. Clemens, C.A. Bondy, Mol. Cell. Neurosci. 3, 36 (1992)
P. Caroni, P. Grandes, J. Cell. Biol. 110, 1307 (1990)
V.B. Schini-Kerth, Transf. Clin. Biolog. 6, 355 (1999)
G. Pete, Y. Hu, M.F. Walsh, J. Sowers, J.C. Dunbar, Proc. Soc. Biol. Med. 213, 187 (1996)
R.H. Boger, C. Skamira, S.M. Bode-Boger, G. Brabant, A. von zur Muhlen, J.C. Frolich, J. Clin. Invest. 98, 2706 (1996)
H. Bai, M.J. Pollman, Y. Inishi, G.H. Gibbons, Circ. Res. 85, 229 (1999)
V.A. Patel, Q.J. Zhang, K. Siddle, M.A. Soos, M. Goddard, P.L. Weissberg, M.R. Bennett, Circ. Res. 88, 895 (2001)
M. Britton, J. Rafols, S. Alousi, J.C. Dunbar, Int. J. Exp. Diabesity Res. 4, 13 (2003)
A.A. Sima, Cell. Mol. Life Sci. 60, 2445 (2003)
K. Asplund, E. Hägg, C. Helmers, F. Lithner, T. Strand, P. Wester, Acta Med. Scand. 207, 417 (1980)
M. Brownlee, A. Cerami, H. Viassara, N. Engl. J. Med. 318, 1315 (1988)
S. Tesfaye, R. Malik, J.D. Ward, Diabetologia 37, 874 (1994)
N.E. Cameron, M.A. Cotter, Diab. Res. Clin. Pract. 45, 137 (1999)
N.N. Rizk, J.A. Rafols, J.C. Dunbar, Brain Res. 1053, 1 (2005)
A.A.F. Sima, C.R. Pierson, J. Clin. Invest. 66, 1226 (2001)
L. Martin, N. Al-Abdulla, A. Brambrink, J. Kirsch, F. Sieber, C. Portera-Cailliau, Brain Res. Bull. 46, 281 (1998)
A.A.F. Sima, W. Zhang, G. Xu, K. Sugimoto, D. Guberski, M.A. Yorek, Diabetologia 43, 786 (2000)
A. Yair, J. Vellis, Brain Res. 406, 32 (1987)
M.A. Aberg, N.D. Aberg, H. Hedbacker, J. Oscarsson, P.S. Eriksson, J. Neurosci. 20, 2896 (2000)
E.Y. Davani, Z. Brumme, K.S. Gurpreet, G.K. Singhera, H.C. Cote, P.R. Harrigan, D.R. Dorscheid, Crit. Care 7, 176 (2003)
H.S. Sharma, Acta Neurochir. Suppl. 86, 383 (2003)
A.A.F. Sima, V. Nathaniel, V. Bril, T. McEwen, D.A. Greene, J. Clin. Invest. 81, 349 (1988)
B.C. White, L.I. Grossman, B.J. O’Neil, D.J. Degracia, R.W. Neumar, J.A. Rafols, G.S. Krause, Ann. Emerg. Med. 27, 588 (1996)
J.A. Rafols, B.J. O’Neil, G.S. Krause, R.W. Neumar, B.C. White, Acta Neuropathol. 90, 17 (1995)
S. Hatashita, J.T. Hoff, Stroke 21, 582 (1990)
R. Veltkamp, D.S. Warner, F. Domoki, A.D. Brinkhous, J.F. Toole, D.W. Busija, Brain Res. 853, 68 (2000)
C.N. Joshi, S.K. Jain, P.R. Murthy, Brain Res. Prot. 13, 11 (2004)
Acknowledgments
Supported by NIH R24 MH047181.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rizk, N.N., Myatt-Jones, J., Rafols, J. et al. Insulin like growth factor-1 (IGF-1) decreases ischemia-reperfusion induced apoptosis and necrosis in diabetic rats. Endocr 31, 66–71 (2007). https://doi.org/10.1007/s12020-007-0012-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-007-0012-0