TY - JOUR
T1 - Neurodegeneration is associated to changes in serum insulin-like growth factors
AU - Busiguina, Svetlana
AU - Fernandez, Ana M.
AU - Barrios, Vicente
AU - Clark, Ruth
AU - Tolbert, Daniel L.
AU - Berciano, Jose
AU - Torres-Aleman, Ignacio
N1 - Funding Information:
We thank Brad Margus and the AT Children’s Project staff for their invaluable help. This study was supported by Grants PM97-0018 from DGESIC, 08.5/0051/98 from CAM and from Fundación Endocrinologia y Nutrición.
PY - 2000
Y1 - 2000
N2 - Serum levels of insulin and insulin-like growth factors and their binding proteins (IGFs and IGFBPs, respectively) are changed in human neurodegenerative diseases of very different etiology, such as Alzheimer's disease, amyotrophic lateral sclerosis, or cerebellar ataxia. However, the significance of these endocrine disturbances is not clear. We now report that in two very different inherited neurodegenerative conditions, ataxia-telangiectasia (AT) and Charcot-Marie-Tooth 1A (CMT-1A) disease, serum levels of IGFs are also altered. Both types of patients have increased serum IGF- and IGFBP-2 levels, and decreased serum IGFBP-1 levels, while only AT patients have high serum insulin levels. Furthermore, serum IGFs are also changed in three different animal models of neurodegeneration: neurotoxin-induced motor discoordination, diabetic neuropathy, and hereditary cerebellar ataxia. In these three models, serum insulin levels are significantly decreased, serum IGF- and IGFBP-1,-2, and -3 are decreased in diabetic and neurotoxin-injected rats, while serum IGFBP-1 is increased in hereditary ataxic rats. Altogether, these observations indicate that a great variety of neurodegenerative diseases show endocrine perturbations, resulting in changes in serum IGFs levels. These perturbations are disease-specific and are probably due to metabolic and endocrine derangements, nerve cell death, and sickness-related disturbances associated to the neurodegenerative process. Our observations strongly support the need to evaluate serum IGFs in other neurodegenerative conditions.
AB - Serum levels of insulin and insulin-like growth factors and their binding proteins (IGFs and IGFBPs, respectively) are changed in human neurodegenerative diseases of very different etiology, such as Alzheimer's disease, amyotrophic lateral sclerosis, or cerebellar ataxia. However, the significance of these endocrine disturbances is not clear. We now report that in two very different inherited neurodegenerative conditions, ataxia-telangiectasia (AT) and Charcot-Marie-Tooth 1A (CMT-1A) disease, serum levels of IGFs are also altered. Both types of patients have increased serum IGF- and IGFBP-2 levels, and decreased serum IGFBP-1 levels, while only AT patients have high serum insulin levels. Furthermore, serum IGFs are also changed in three different animal models of neurodegeneration: neurotoxin-induced motor discoordination, diabetic neuropathy, and hereditary cerebellar ataxia. In these three models, serum insulin levels are significantly decreased, serum IGF- and IGFBP-1,-2, and -3 are decreased in diabetic and neurotoxin-injected rats, while serum IGFBP-1 is increased in hereditary ataxic rats. Altogether, these observations indicate that a great variety of neurodegenerative diseases show endocrine perturbations, resulting in changes in serum IGFs levels. These perturbations are disease-specific and are probably due to metabolic and endocrine derangements, nerve cell death, and sickness-related disturbances associated to the neurodegenerative process. Our observations strongly support the need to evaluate serum IGFs in other neurodegenerative conditions.
KW - Ataxia
KW - Charcot-Marie-Tooth disease
KW - Diabetes
KW - Insulin-like growth factors
KW - Neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=0034520593&partnerID=8YFLogxK
U2 - 10.1006/nbdi.2000.0311
DO - 10.1006/nbdi.2000.0311
M3 - Article
C2 - 11114263
AN - SCOPUS:0034520593
VL - 7
SP - 657
EP - 665
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 6
ER -