Subject Index. neuronal survival promotion by insulinlike growth factor-i , 162 regulatory proteins 148, 162

Transcription

1 Subject Index Acid-labile subunit (ALS) evaluation 84 function 84 growth hormone activity marker 91 growth hormone insensitivity levels 102, 104 Alzheimer s disease, insulin-like growth factor-i neuroprotection 148 Amyotrophic lateral sclerosis (ALS) epidemiology 160 etiology 161 glutamate excitotoxicity 162, 163 inflammatory cytokines 162 binding protein levels 164, 165 neuroprotection 148 serum levels 164 therapy clinical trials 151, 153, 163, 164 prospects rationale neuronal apoptosis 162 oxidative stress 163 pathology 161 serpins in pathogenesis 165 Anorexia nervosa, insulin-like growth factor-i deficiency 104 Apoptosis amyotrophic lateral sclerosis 162 mesenchymal stem cell assay and IGFBP-3 induction 25, 27 neuronal survival promotion by insulinlike growth factor-i , 162 regulatory proteins 148, 162 Beta cell, insulin-like growth factor effects on growth, survival, and function 46, 47 Cancer knockout mouse studies 14 mediation of neuroblastoma motility 141, 143, 144 insulin-like growth factor system 13, 14 Cartilage IGFBP-3 effects role 20, 21 mesenchymal stem cell therapy, see Mesenchymal stem cell Caspases, regulation 150, 151 Chondrogenesis IGFBP-3 effects role 20, 21 mesenchymal stem cell therapy, see Mesenchymal stem cell overview 17, 18 Coronary heart disease, insulin-like growth factor-i cardiac benefits 48 deficiency and risks Mendelian randomization in risk assessment 50,

2 Crohn s disease, deficiency 104 Cystic fibrosis, deficiency 104 Diabetes typ 1 growth hormone insulin resistance role levels 107, 108 microvascular complication role IGFBP-1 levels 108 IGFBP-3 levels 107 replacement therapy 114, 116 insulin resistance role levels 107 microvascular complication role replacement therapy adverse events IGFBP-3 combination therapy 114, 116 prospects 116, 117 rationale 112 trials 113 Diabetes type 2 epidemiology 124 beta cell growth, survival and function effects 46, 47 deficiency 45, 47 gene polymorphisms 47 insulin sensitivity response 45, 46 knockout mouse studies 46 Mendelian randomization in risk assessment 50, 51 therapy IGFBP-3 combination therapy 129, 130 insulin resistance trials prospects rationale 125, 126 safety 128, 129 management 124 Diabetic neuropathy, insulin-like growth factor-i neuroprotection 148 ERK/MAPK pathway signaling in nervous system 137, 161, 163 neurite outgrowth mediation and nerve injury relevance 139, 141 neuronal motility mediation and neuroblastoma 141, 143, 144 neuroprotective signaling 150 Growth hormone (GH) biochemical markers of action diabetes type 1 insulin resistance role levels 107, 108 microvascular complication role role in action 1, 12 secretion 55, 56 secretion relationship to plasma 57, 58 therapy, see Growth hormone deficiency Growth hormone deficiency (GHD) auxological and biochemical assessment of children 72, 73 cardiac dysfunction 48 diagnosis adults children 66, 67 overview 3 5, 76, 77 epidemiology 3 growth hormone therapy in adult growth hormone deficiency biochemical markers of action dose response 94, 95 dosing 89, 90 monitoring adolescent-to-adult transition phase 96, 97 advantages and limitations 97, 98 dose titration 95 elderly patients 95, 96 safety marker 92 young adults 97 sex differences in response 93, 94 IGFBP-3 evaluation Subject Index 172

3 insulin-like growth factor generation tests childhood-onset growth hormone deficiency 67, 68 evaluation 6, 7 growth hormone therapy monitoring 7, 8, 92 responsiveness versus deficiency 5 Growth hormone insensitivity (GHI) acid-labile subunit levels 102, 104 acquired insensitivity due to chronic pediatric illness 104 idiopathic short-stature patients 103 IGFBP-3 deficiency deficiency partial growth hormone insensitivity markers 102, 103 receptor mutations 101, 103 Hypertriglyceridemia, insulin-like growth factor-i response 127 Hypoxic-ischemic encephalopathy causes 31 delayed neuronal injury 32, 41 induction after injury 32 neuroprotection mechanisms IGFBP mediation 39, 40 indirect effects 41 receptor mediation 39 N-terminal peptide neuroprotection studies 40, 41 neuroprotection studies in animal models brain region selectivity 33, 34 dose dependence 32, 33 progressive neuronal injury and functional recovery 36, 37 therapeutic window 35, 36 white matter protection 37, 38 therapeutic prospects 41, 42 Idiopathic short stature (ISS), growth hormone insensitivity 103 IGFBP-1 (insulin-like growth factor binding protein-1) diabetes type 1 levels 108 diabetes type 2 levels 47 IGFBP-2 (insulin-like growth factor binding protein-2) hypoxic-ischemic encephalopathy role 39, 40 levels in growth hormone deficiency 58 IGFBP-3 (insulin-like growth factor binding protein-3) evaluation 84 cartilage effects childhood-onset growth hormone deficiency evaluation diabetes type 1 levels 107 replacement therapy 114, 116 generation tests in growth hormone deficiency evaluation 6, 7, 77 growth hormone therapy monitoring 7, 8 growth hormone activity marker 91, 92 growth hormone insensitivity and deficiency combination therapy for insulin resistance 129, 130 sensitivity and specificity in growth hormone deficiency evaluation 72 Insulin, growth hormone activity marker 91 Insulin-like growth factor deficiency (IGFD) assays 4 coronary heart disease risks diabetes type 2, see Diabetes type 2 therapy 8, 9 management 4, 5 primary versus secondary causes 4 Insulin-like growth factor-i (IGF-I) amyotrophic lateral sclerosis trials, see Amyotrophic lateral sclerosis assays evaluation childhood-onset growth hormone deficiency evaluation 67, 68 Subject Index 173

4 Insulin-like growth factor-i (IGF-I) (continued) assays (continued) clinical use discrepancies 56, 57 growth hormone secretion relationship to plasma insulin-like growth factor-i 57, 58 interpretation problems 63, 64 sensitivity and specificity in growth hormone deficiency evaluation 72 technical problems variations of levels in normal subjects 58, 59 beta cell growth, survival and function effects 46, 47 binding proteins, see specific IGFBPs cartilage role 20, 21 coronary heart disease role diabetes and deficiency, see Diabetes type 1; Diabetes type 2 growth hormone action role 1, 12 activity marker 91, 92 therapy monitoring, see Growth hormone deficiency growth hormone insensitivity and deficiency ischemic brain injury studies, see Hypoxic-ischemic encephalopathy knockout mice cancer studies 14 chondrocyte defects 21 insulin resistance studies 14, 15, 46 liver-derived insulin-like growth factor-i gene deletion 12, 13 nervous system effects 139 prospects for study 16 receptor knockout mouse and growth effects 2 nervous system effects, see Nervous system, effects Insulin resistance diabetes type 1 pathophysiology clinical trials knockout mouse studies 14, 15, 46 severe spectrum 122 Insulin tolerance test (ITT), adult growth hormone deficiency diagnosis 76, 78 Ischemic brain injury, see Hypoxicischemic encephalopathy Juvenile chronic arthritis, insulin-like growth factor-i deficiency 104 Laron syndrome, see Growth hormone insensitivity Leptin, growth hormone activity marker 91 Mesenchymal stem cell (MSC) cartilage disease therapy 20 chondrogenesis studies of insulin-like growth factor system effects apoptosis assay and IGFBP-3 induction 25, 27 chondrocyte differentiation 18, 19 human cell isolation, expansion, and micromass pellet formation 24, 25 IGFBP-3 inhibitory effects 27, 28 effects on chondrogenic pellet size 27 mouse cell isolation, expansion, and micromass pellet formation 23, 24 prostaglandin synthesis assay and transforming growth factor- effects RCJ3.1C5.18 cell culture 25 statistical analysis 26 gene and cell therapy advantages 18, 19 implantation studies 19, 20 in chondrogenic potential 19 markers 19 plasticity 19 Motor neuron disease, see Amyotrophic lateral sclerosis Multiple sclerosis, insulin-like growth factor-i treatment prospects 144, 145, 147 Myelination, promotion 144, 145, 147 Subject Index 174

5 Nervous system, insulin-like growth factor-i effects amyotrophic lateral sclerosis trials, see Amyotrophic lateral sclerosis myelination and demyelinating diseases 144, 145, 147 neurite outgrowth mediation and nerve injury relevance 137, 139, 141 neurological disease treatment prospects 151, 153 neuronal loss in neurological disease 135, 136, neuronal motility mediation and neuroblastoma 141, 143, 144 neuronal survival promotion signaling pathways 137, 161, 163 trophic support in neurological disease 136, 137 Parkinson s disease, insulin-like growth factor-i neuroprotection 148 Phosphatidylinositol 3-kinase/Akt pathway signaling in nervous system 137 neurite outgrowth mediation and nerve injury relevance 139, 141 neuroprotective signaling Prostaglandins, mesenchymal stem cell synthesis assay and transforming growth factor- effects RCJ3.1C5.18 cells, culture 25 Serpins, amyotrophic lateral sclerosis pathogenesis 165 Somatomedin hypothesis, historical perspective 12, 21 Transforming growth factor- (TGF- ), mesenchymal stem cell prostaglandin synthesis effects Subject Index 175

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