Index. A Acetylcholine, 47 Adenosine triphosphate (ATP) release, from RBCs, 18 20, 23 Advanced glycation end products (AGEs), proatherogenic

Transcription

1 A Acetylcholine, 47 Adenosine triphosphate (ATP) release, from RBCs, 18 20, 23 Advanced glycation end products (AGEs), proatherogenic effects, 153 Afferent and efferent arteriolar tone, Alzheimer s disease, and diabetic encephalopathy, 101 Amyloid precursor proteins (APP) metabolism and phospho-tau expression, 101, 102 Anti-inflammatory properties internalization, in vascular cells, 120, 121 encephalopathy, 119 intracellular signaling pathways nuclear factor (NF)- k B pathway, PPAR-g, ischemia/reperfusion, 119 sepsis, vascular disease, 113, 114 and vascular dysfunction, in type 1 diabetes and endothelial function, 115 endothelial cells, effects on, inflammation and endothelial dysfunction, smooth muscle cells, effects on, Aortic smooth muscle cells (AoSMCs), 118 Asymmetric dimethylarginine (ADMA), 56 Atherogenesis, 140, 154, 157 Atherosclerotic lesions, Axoglial junction loss, morphometric assessment, 83, 84 Axonal atrophy, B Blood flow. See Microvascular blood flow regulation C CD4-positive cells, in vessel wall, 155 Cell membrane interaction, with, 161, 162 Chemotactic activity, of, 155 Combined and zinc, cellular function as biologically-active substance, bloodstream, cells in ATP release, from RBCs, 23 endothelium, 23, 24 leukocyte, 24 NO production, 24, 25 platelet, 24, 25 metal binding, discovery of ATP release, from RBCs, 20 Cr3+ salt, 20, 21 mass spectrometric analysis, 20 ph, hexameric insulin disaggregation, 22 zinc activation, mechanism for, 21, 22 RBC, as blood flow determinant, 17 vasculature ATP effects, nitric oxide (NO), 18 vasodilation, 18 Coronary artery bypass grafting (CABG), 130 D Diabetic encephalopathy, type 1 animal studies of, 94 in children, 93 clinical studies functional and neuropsychological findings, 94 imaging studies, evoked potentials, 94 experimental studies glucose metabolism, RAGE, and inflammatory responses, 100, 101 insulin-signaling and, 96 MicroPet data, BB/Wor-rats, 100 neurobehavioral deficits, neurodegenerative changes, neurotrophism and synaptic alterations, streptozotocin-induced diabetes, in rodents, white matter changes, gray matter, 95, 103, 105 metabolic and structural abnormalities, 104, 105 white matter atrophy, 94, 103 A.A.F. Sima (ed.), Diabetes & C-Peptide: Scientifi c and Clinical Aspects, Contemporary Diabetes, DOI / , Springer Science+Business Media, LLC

2 166 Index Diabetic nephropathy ameliorating effect of, 58 E-cadherin expression, in HK 2 cells, enos expression modification, 59 fibrosis, 38 hepatocyte growth factor (HGF), neutralization of, 38, 40 Na+/K+-ATPase expression and activity, NF-k B, 37, 38 NO availability, enos regulation, retinoic acid and hepatocyte growth factor Snail expression, 40 TGF-b 1, 38, 39 TNF-a, 37, 38 in tubular cells, enos activity, regulation of, expression in, NO-eNOS system, 60, 61 oxidative stress, 57 streptozotocin, 55, 58 type 1 diabetes, renoprotective effects, Diabetic neuropathy, type 1 diabetes clinical studies on and nerve function erectile function, 148, 149 heart rate variability (HRV), 148, 149 and placebo administration, sural nerve conduction velocity (SCV), 147, 148 vibration perception threshold and neuropathy assessment score, median changes in, 148, 149 definition of, 145 distal symmetric polyneuropathy (DSPN), 145 pathogenesis of, 146 peripheral nerve function and structure, 146 signs of, 145 treatment of replacement therapy, 149, 150 pharmaceutical therapy, 150 Diabetic polyneuropathy (DPN) axonal degeneration, 82, 86, 88 characteristics of, 79 clinical trials, 80 altered neurotrophism, axoglial junction loss, morphometric assessment of, 83, 84 b -tubulin, time sequence of, 88 early dysmetabolism and acute nerve conduction defect, and insulin interaction, nerve fiber regeneration, 87, 88 neuroskeletal proteins and axonal atrophy, nociceptive neuropathy and, nodal and paranodal degeneration, 83 unmyelinated C-fibers, morphometric analyses of, 86 hyperglycemia, 80 insulin action, 80 pathogenesis of, 79 Dimethylarginine dimethylaminohydrolases (DDAHs), 56 Distal symmetric polyneuropathy (DSPN), 145, 150 E E-cadherin expression, in HK 2 cells, Encephalopathy, anti-inflammatory properties, 119 Endothelial cells, effects on, 23, 24 anti-inflammatory activity of, 115, 116 arterial endothelial cell layer, 115 HAEC, U937 adhesion, 116, 117 Endothelial dysfunction, inflammation and, Endothelial function, anti-inflammatory properties, 115 Endothelial nitric oxide synthase (enos), activators and inhibitors of, 46 diabetic nephropathy activity, regulation of, expression in, expression modification in, 59 Erectile function, diabetic neuropathy, 148, 149 Erythrocyte deformability, microvascular blood flow, 49, 50 Extracellular signal-regulated kinase (ERK) activation, 34, 35 F Flow mediated vasodilatation (FMD), 47 G Gel electrophoresis, peptide interactions, Glomerular filtration rate (GFR), 55 regulators of, 68 Glomerulus hyperfiltration, 69, 72, 73 volume and mesangial matrix expansion, 72 Glucose metabolism, type 1 diabetic encephalopathy, 100, 101 GluR2, type 1 diabetic encephalopathy, 99, 100 GLUT1, 57 H Heart rate variability (HRV), diabetic neuropathy, 148, 149 Hepatocyte growth factor (HGF), diabetic nephropathy neutralization of, 38, 40 High glucose-stimulated aortic endothelial cells (HAEC), U937 adhesion, 116, 117 Hyperglycemia effect, on vascular wall, 114

3 I Inflammation cells, intracellular signaling pathways, and endothelial dysfunction, in T1D adhesion molecules, 113 hyperglycemia effect, on vascular wall, 114 innate immune system role in, 112 long-term complications, small and large vessels, monocytes, 112, 113 oxidative stress, 114 vascular dysfunction, components of, 113 responses, type 1 diabetic encephalopathy, 100, 101 Insulin biosynthesis of, 1 2 convertases, 2 acidic residues, 2 clearance, from blood, 3 4 functions of, 4 interaction with, 80 81, 162 levels, 1 zinc binding, 2, 3 macrovascular complications clinical studies, 130 neointima formation in vivo and in vitro, vascular smooth muscle cell proliferation and migration, 132 mutations, human preproinsulin, 2, 3 oligomers desaggregation, chaperone-like manner, 9 10 proinsulin, 1, 2 signaling and, type 1 diabetic encephalopathy, 96 Ischemia/reperfusion, 119 K Kidney, signaling, 161 cellular signaling effects of, 41 diabetic nephropathy, pathophysiology of E-cadherin expression, in HK 2 cells, fibrosis, 38 hepatocyte growth factor (HGF), neutralization of, 38, 40 NF-k B, 37, 38 retinoic acid and hepatocyte growth factor Snail expression, 40 TGF-b 1, 38, 39 TNF-a, 37, 38 in tubular cells, and enos, MAPKs stimulation ERK activation, 34, 35 opossum kidney (OK) cells, 34 pathways, 36 and Na +,K + -ATPase activity, 33 oxygenation, 71 PI 3-kinase activation, 36 signaling elements, structure-function relationships, transcription factors, L Leukocyte, microvascular blood flow, M Macrophages differentiation, proatherogenic effects, 156 Macrovascular complications, diabetes atherogenesis, 140 cellular effects, of vascular endothelial cells, vascular smooth muscle cells, 135 coronary artery disease (CAD), 129 internalisation and intracellular localisation, 139 s functional effects, mechanisms of binding and cellular internalisation, 136 MAPK, 136 SREBP 1, insulin, role of clinical studies, 130 neointima formation in vivo and in vitro, vascular smooth muscle cell proliferation and migration, 132 mtor, 139 proinsulin, revascularisation in, SV-SMC migration, 139 Mass spectra, peptide interactions, 10, 13 Microvascular blood flow regulation, effects of in forearm, 48 in skin, supplementation, endothelial dysfunction, 45 endothelial function, 45 erythrocyte deformability, shear stress, 49, 50 functional alterations in, 49 insulin resistant type 2 diabetic patients, 51 leukocyte, 50 microcirculation, 46, 48, 51 molecular effects, of, 51 nitric oxide (NO) acetylcholine, 47 enos, activators and inhibitors of, 46 flow mediated vasodilatation (FMD), 47 NG -nitro-l-arginine (l-nna) and Ca 2+ -free Locke s solution, effect of, 47 vasorelaxation, 46 type 1 diabetes, 45, 46, 49 Mitogen activated protein kinases (MAPKs) stimulation, in kidney, Monocytes, 112, 113 differentiation, proatherogenic effects, 156 in vessel wall, 155 Morris water maze method, neurobehavioral deficits, 97, 98

4 168 Index N Na + /K + -ATPase activity, 81, 82 and expression, in diabetic nephropathy, in kidney, 33 Nerve conduction defect and early dysmetabolism, Nerve conduction velocity (NCV), 81, 82 Nerve fiber regeneration, 87, 88 Neurobehavioral deficits, type 1 diabetic encephalopathy longitudinal assessments, Morris water maze method, 97, 98 radial arm paradigm, 97 Neurodegenerative changes, type 1 diabetic encephalopathy Alzheimer s disease, 101 amyloidogenic APP metabolism and phospho-tau expression, 101, 102 antiapoptotic effects, 102 Neuroskeletal proteins and axonal atrophy, Neurotrophism diabetic encephalopathy, type 1, diabetic polyneuropathy neurotrophic factor receptors, protein expression of, 84, 85 NGF, concentration of, 83, 84 Nitric oxide (NO), 17, 18, 24, 25, 133 availability, enos regulation, microvascular blood flow regulation, Nociceptive neuropathy, Nodal and paranodal degeneration, 83 Nuclear factor (NF)-kB, anti-inflammatory activity, 122 phosphorylation cascade, 123 proteasome, 123 O Oligomer formations, of, 10 peptide interactions, 9 Oxidative stress, 114 in diabetic nephropathy, 57 P Peptide interactions, of proinsulin aggregation and fibrillation of, amyloid-like properties, 12, 14 Biacore chip-attached, 9 cellular internalization, 8 9 conservation pattern for, 8 and slow onset of, 13, 14 depository tendency of, 14 gel electrophoresis, heterointeractions, 11 homooligomers, insulin oligomers desaggregation, chaperone-like manner, 9 10 synthesis and secretion, 7 mass spectra, 10, 13 oligomer formations of, 10 peptide interactions, 9 plasma insulin, 11 precaution, reaction-like transitions, 11 in receptor-like cellular binding, 7 8 surface plasmon resonance, 11, 13 tri-partite correlation, 14, 15 type 2 diabetes, 14 Peripheral nerve, 161 function and structure, diabetic neuropathy, 146 Peroxisome-proliferator-activated receptor g (PPAR-g ), 37, ph, hexameric insulin disaggregation, 22 Phosphatidylinositide 3-kinase (PI 3-kinase) activation, in kidney, 36 Platelet, 24, 25 Polymorphonuclear leukocyte (PMN) infiltration, 119 Presynaptic synaptophysin, type 1 diabetic encephalopathy, 99 Proatherogenic effects, of advanced glycation end products (AGEs), 153 atherogenesis, 154 CD4-positive cells and monocytes, in vessel wall, 155 and chemotactic activity, 155 deposits in vascular wall, of atherosclerotic lesions, intracellular localization, intracellular signaling pathways, in inflammatory cells, monocytes/macrophages differentiation, 156 renal and nerve dysfunction, 153 restenosis and atherogenesis formation, SMCs role in, 157 smooth muscle cell proliferation, T-cell, 155, 156 in type 1 and type 2 diabetes, 158 Proinsulin, 1, 2, Protein kinase C (PKC), 59, 60 R Reactive oxygen species (ROS), 57, 114 Receptor for advanced glycation end products (RAGE), type 1 diabetic encephalopathy, 100, 101 Red blood cell (RBC) ATP release, 18 20, 23 as blood flow determinant, 17 Renal system anatomy and physiology, structural abnormalities and, tubules and tubular cells, Renoprotective effects, type 1 diabetes afferent and efferent arteriolar tone, 69 70, 74 administration, glomerular hyperfiltration, 72, 73

5 169 for advanced renal dysfunction, chronic administration, urinary albumin excretion, 73 clinical trials, 75 in experimental diabetes, 69 glomerular volume and mesangial matrix expansion, 72 kidney oxygenation, 71 and renal structural abnormalities, diabetic nephropathy, glomerular filtration, regulators of, 68 glomerular hyperfiltration, 69 oxygen consumption, 70, 71 renal anatomy and physiology, renal tubules and tubular cells, tubular Na + reabsorption and Li + clearance, 70, 71 Reperfusion injury, 119 Restenosis formation, SMCs role in, 157 Retinoic acid and hepatocyte growth factor signaling, diabetic nephropathy, 39 Revascularisation, in macrovascular complications, ROS. See Reactive oxygen species (ROS) S Sepsis, Skin microvascular blood flow, Smooth muscle cells effects on, proliferation, restenosis and atherogenesis formation, 157 Snail expression, diabetic nephropathy, 40 Sterol regulatory element-binding protein 1 (SREBP 1) gene silencing, 137 insulin induced, mediators of, 138 real-time RT-PCR data, mrna levels, 136, 137 Streptozotocin diabetic encephalopathy, type 1, diabetic nephropathy, 55, 58 Sural nerve conduction velocity (SCV), 147, 148 Synaptic alterations, type 1 diabetic encephalopathy, T Transcription factors, Transforming growth factor-b1 (TGF-b1), diabetic nephropathy, 38, 39 b -Tubulin, nerve fiber regeneration, 88 Tumor necrosis factor-a (TNF-a ), diabetic nephropathy, 37, 38 Type 1 diabetes animal models, clinical effects of, 161 levels, 162 replacement, inflammation and endothelial dysfunction in, microvascular blood flow regulation, 45, 46, 49 renoprotective effects ( see Renoprotective effects, type 1 diabetes) U Urinary albumin excretion, 73 V Vascular cells, internalization, 120, 121 Vascular dysfunction, in type 1 diabetes and endothelial function, 115 endothelial cells, effects on, inflammation and endothelial dysfunction, smooth muscle cells, effects on, Vascular endothelial cells, 134, 135 nitric oxide (NO), 133 Vascular smooth muscle cells (VSMCs), , 135 proliferation and migration, 132 restenosis and atherogenesis formation, 157 Vasculature, combined and zinc ATP effects, nitric oxide (NO), 18 vasodilation, 18 W White matter changes, type 1 diabetic encephalopathy, Z Zinc. See Combined and zinc, cellular function