scholarly journals Circulating insulin-like growth factor I is involved in the effect of diet on peripheral amyloid β clearance

2020 ◽  
Author(s):  
Raquel Herrero-Labrador ◽  
Angel Trueba-Saiz ◽  
Laura Martinez-Rachadell ◽  
Maria Estrella Fernandez de Sevilla ◽  
Jonathan A Zegarra-Valdivia ◽  
...  
Keyword(s):  
Growth Factor ◽  
Amyloid Β ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Peripheral Clearance ◽  
Aβ Clearance ◽  
Growth Factor I ◽  
The Brain

Abstract BackgroundObesity is a risk factor for Alzheimer´s disease (AD), but underlying mechanisms are not clear.MethodsWe analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact on brain Aβ load, a major landmark of AD pathology. We also analyzed whether circulating insulin-like growth factor I (IGF-I) intervenes in the effects of overweight as this growth factor modulates brain Aβ clearance, and is increased in serum of overweight mice. Results Overweight mice showed increased peripheral Aβ clearance by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. We also found that Aβ clearance by hepatocytes is stimulated by IGF-I, and that mice with low serum IGF-I levels show reduced peripheral Aβ clearance and unchanged brain Aβ levels. In the brain, IGF-I favored association of its receptor (IGF-IR) with Aβ precursor protein (APP), and at the same time stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly reduced brain IGF-IR phosphorylation and APP/IGF-IR association was found in overweight mice as compared to lean controls. Conclusions Collectively, these results indicate that diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ clearance probably because its brain entrance is reduced.

scholarly journals DIET INFLUENCES PERIPHERAL AMYLOID β METABOLISM: A ROLE FOR CIRCULATING INSULIN-LIKE GROWTH FACTOR I

2020 ◽  
Author(s):  
R. Herrero-Labrador ◽  
A. Trueba-Saiz ◽  
L. Martinez-Rachadell ◽  
E. Fernandez de Sevilla ◽  
S. Diaz-Pacheco ◽  
...  
Keyword(s):  
Growth Factor ◽  
Amyloid Β ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Peripheral Clearance ◽  
Aβ Clearance ◽  
Growth Factor I ◽  
The Brain

AbstractObesity is a risk factor for Alzheimer’s disease (AD), but underlying mechanisms are not clear. We analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact on brain Aβ load, a major landmark of AD pathology. Overweight mice showed increased peripheral Aβ clearance by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. Since circulating insulin-like growth factor I (IGF-I) modulates brain Aβ clearance, and is increased in serum of overweight mice, we determined whether it affects peripheral Aβ clearance. We found that Aβ uptake by hepatocytes is stimulated by IGF-I. Moreover, mice with low serum IGF-I levels show reduced peripheral Aβ clearance. In the brain, IGF-I favored association of its receptor (IGF-IR) with Aβ precursor protein (APP), and at the same time stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly less activation of brain IGF-IR phosphorylation and APP/IGF-IR association was found in overweight mice as compared to lean controls. Collectively, these results indicate that diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ clearance probably because its brain entrance is reduced.

scholarly journals Circulating Insulin-Like Growth Factor I is Involved in the Effect of High Fat Diet on Peripheral Amyloid β Clearance

2020 ◽  
Vol 21 (24) ◽  
pp. 9675
Author(s):  
Raquel Herrero-Labrador ◽  
Angel Trueba-Saiz ◽  
Laura Martinez-Rachadell ◽  
Mᵃ Estrella Fernandez de Sevilla ◽  
Jonathan A. Zegarra-Valdivia ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Fat Diet ◽  
Amyloid Β ◽  
Insulin Like Growth Factor ◽  
High Fat ◽  
Factor I ◽  
Igf I ◽  
Peripheral Clearance ◽  
Aβ Clearance ◽  
The Brain

Obesity is a risk factor for Alzheimer’s disease (AD), but underlying mechanisms are not clear. We analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact brain Aβ load, a major landmark of AD pathology. We also analyzed whether circulating insulin-like growth factor I (IGF-I) intervenes in the effects of overweight as this growth factor modulates brain Aβ clearance and is increased in the serum of overweight mice. Overweight mice showed increased Aβ accumulation by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. We also found that Aβ accumulation by hepatocytes is stimulated by IGF-I, and that mice with low serum IGF-I levels show reduced liver Aβ accumulation—ameliorated by IGF-I administration, and unchanged brain Aβ levels. In the brain, IGF-I favored the association of its receptor (IGF-IR) with the Aβ precursor protein (APP), and at the same time, stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly reduced brain IGF-IR phosphorylation and APP/IGF-IR association were found in overweight mice as compared to lean controls. Collectively, these results indicate that a high-fat diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ load probably because its brain entrance is reduced.

Intranasal delivery of erythropoietin plus insulin-like growth factor–I for acute neuroprotection in stroke

2009 ◽  
Vol 111 (1) ◽  
pp. 164-170 ◽  
Author(s):  
Lauren Fletcher ◽  
Sanjivan Kohli ◽  
Shane M. Sprague ◽  
Robert A. Scranton ◽  
Stuart A. Lipton ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intranasal Administration ◽  
Neuronal Damage ◽  
Intraperitoneal Administration ◽  
Insulin Like Growth Factor ◽  
Efficient Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
The Brain

Object Individually, the cytokines erythropoietin (EPO) and insulin-like growth factor–I (IGF-I) have both been shown to reduce neuronal damage significantly in rodent models of cerebral ischemia. The authors have previously shown that EPO and IGF-I, when administered together, provide acute and prolonged neuroprotection in cerebrocortical cultures against N-methyl-d-aspartate–induced apoptosis. The aim of this study was to determine whether intranasally applied EPO plus IGF-I can provide acute neuroprotection in an animal stroke model and to show that intranasal administration is more efficient at delivering EPO plus IGF-I to the brain when compared with intravenous, subcutaneous, or intraperitoneal administration. Methods The EPO and IGF-I were administered intranasally to mice that underwent transient middle cerebral artery occlusion (MCAO). Stroke volumes were measured after 1 hour of MCAO and 24 hours of reperfusion. To evaluate the long-term effects of this treatment, behavioral outcomes were assessed at 3, 30, 60, and 90 days following MCAO. Radiography and liquid scintillation were used to visualize and quantify the uptake of radiolabeled 125I-EPO and 125I–IGF-I into the mouse brain after intranasal, intravenous, subcutaneous, or intraperitoneal administration. Results Intranasal administration of EPO plus IGF-I reduced stroke volumes within 24 hours and improved neurological function in mice up to 90 days after MCAO. The 125I-EPO and 125I–IGF-I were found in the brain within 20 minutes after intranasal administration and accumulated within the injured areas of the brain. In addition, intranasal administration delivered significantly higher levels of the applied 125I-EPO and 125I–IGF-I to the brain compared with intravenous, subcutaneous, or intraperitoneal administration. Conclusions The data demonstrate that intranasal EPO plus IGF-I penetrates into the brain more efficiently than other drug delivery methods and could potentially provide a fast and efficient treatment to prevent chronic effects of stroke.

scholarly journals Evidence for modulation of osteocalcin containing gamma-carboxyglutamic acid residues synthesis by insulin-like growth factor-I and vitamin K2 in human osteosarcoma cell line MG-63

1998 ◽  
pp. 443-448 ◽  
Author(s):  
Y Kudo ◽  
M Iwashita ◽  
Y Takeda ◽  
T Muraki
Keyword(s):  
Growth Factor ◽  
Vitamin K2 ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Concentration Dependent Manner ◽  
Factor I ◽  
Carboxyglutamic Acid ◽  
Igf I ◽  
Growth Factor I

The effect of insulin-like growth factor-I (IGF-I) and 2-methyl-3-all-trans-tetraphenyl-1,4-naphtoquinone (vitamin K2) on the synthesis of osteocalcin containing gamma-carboxyglutamic acid (Gla) residues which is the physiologically relevant form in bone metabolism was studied in cultured human osteoblast-like (MG-63) cells. Both IGF-I and vitamin K2 stimulated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced osteocalcin containing Gla secretion in a concentration-dependent manner. This stimulatory effect of IGF-I and vitamin K2 was additive. Vitamin K2-enhanced osteocalcin containing Gla secretion was selectively suppressed by 3-(alpha-acetonyl-benzyl)-4-hydroxy-coumarin (warfarin). The stimulatory effect of IGF-I was completely abolished by the presence of cycloheximide; in contrast the effect of vitamin K2 was still observed in the presence of cycloheximide. Treatment of MG-63 cells with IGF-I caused an approximately 2.2-fold increase in osteocalcin mRNA levels (determined by reverse transcription-polymerase chain reaction). Vitamin K2 had no effect on either the stimulation of mRNA level by IGF-I or the basal level. IGF-I-stimulated osteocalcin containing Gla secretion was inhibited by one of its binding proteins (insulin-like growth factor binding protein-4) in a concentration-dependent manner. These findings suggest that the modes of action of IGF-I and vitamin K2 on 1.25(OH)2D3-induced osteocalcin containing Gla secretion in MG-63 cells are different.

Effects of insulin-like growth factor-I and insulin on the in-vitro uptake of sulphate by eel branchial cartilage: evidence for the presence of independent hepatic and pancreatic sulphation factors

1992 ◽  
Vol 133 (2) ◽  
pp. 211-219 ◽  
Author(s):  
C. Duan ◽  
T. Hirano
Keyword(s):  
Growth Factor ◽  
Coho Salmon ◽  
Bovine Insulin ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Cartilage Growth ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT The possible roles of insulin-like growth factor-I (IGF-I) and insulin in regulating cartilage growth were studied in the teleost Anguilla japonica. Significant sulphation activity was found in the extracts of pancreas, liver and muscle, but not in those of kidney, intestine or spleen. The hepatic sulphation activity was significantly decreased by hypophysectomy or by fasting for 14 days, suggesting that this activity is regulated by pituitary function and nutritional status. Northern blot analysis revealed that the hepatic IGF-I mRNA in the eel consists of a major 4·0 kb band. This mRNA was GH-dependent and was significantly decreased by fasting for 14 days. On the other hand, fasting for 14 days had no significant effect on pancreatic sulphation activity. Pancreatic extracts from both intact and hypophysectomized eels exhibited equally significant stimulating activity. Addition of bovine or human insulin (1–250 ng/ml) to the culture medium significantly stimulated sulphate uptake in a dose-dependent manner. Teleost (coho salmon) insulin was as effective as bovine insulin. Bovine insulin was more effective than IGF-I at lower concentrations (1–4 ng/ml) but less effective at higher concentrations (10–250 ng/ml). These results indicate that not only IGF-I but also insulin are likely to be involved in the regulation of cartilage growth in the eel. Journal of Endocrinology (1992) 133, 211–219

scholarly journals Insulin-like growth factor I and insulin induce adipogenic-related gene expression in fetal brown adipocyte primary cultures

1996 ◽  
Vol 319 (2) ◽  
pp. 627-632 ◽  
Author(s):  
Teresa TERUEL ◽  
Angela M VALVERDE ◽  
Manuel BENITO ◽  
Margarita LORENZO
Keyword(s):  
Growth Factor ◽  
Fatty Acid Synthase ◽  
Brown Adipocyte ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Brown Adipocytes ◽  
Factor I ◽  
Fetal Rat ◽  
Igf I ◽  
Growth Factor I

Fetal rat brown adipocytes show high-affinity binding sites for both insulin-like growth factor I (IGF-I) and insulin. Cell culture for 24 h in the presence of IGF-I or insulin, independently, up-regulated the mRNA expression of adipogenic-related genes, such as fatty acid synthase (FAS), glycerol-3-phosphate dehydrogenase and insulin-regulated glucose transporter Glut4, and down-regulated the expression of phosphoenolpyruvate carboxykinase mRNA in a dose-dependent manner. Moreover, both IGF-I and insulin increased the FAS gene transcription rate at 2 h, producing a time-dependent accumulation of FAS mRNA. Furthermore IGF-I or insulin increased glucose uptake and lipid content throughout the 24 h culture period. Our results suggest that both IGF-I and insulin are major signals involved in initiating and/or maintaining the expression of adipogenic-related genes in fetal rat brown adipocytes.

scholarly journals Interdependence of oestrogen and insulin-like growth factor-I in the brain: potential for analysing neuroprotective mechanisms

2005 ◽  
Vol 185 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Pablo Mendez ◽  
Iñigo Azcoitia ◽  
Luis Miguel Garcia-Segura
Keyword(s):  
Growth Factor ◽  
Glycogen Synthase ◽  
Reproductive Behaviour ◽  
Mitogen Activated Protein Kinase ◽  
Neural Function ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
The Brain

The actions of oestradiol in the brain involve interaction with growth factors, such as insulin-like growth factor-I (IGF-I). Many cells in the brain co-express receptors for oestradiol and IGF-I and both factors interact to regulate neural function. The relationship of oestrogen receptor α with IGF-I receptor through the mitogen-activated protein kinase and the phosphoinositide 3-kinase signalling pathways may represent the point of convergence used by these two factors to cooperatively modulate neuritic growth, synaptic plasticity, neuroendocrine events, reproductive behaviour and neuronal survival. In addition, Akt and glycogen synthase kinase 3β are key molecular targets to explain the interaction of oestrogen and IGF-I receptor signalling in the promotion of neuroprotection.

scholarly journals Gq-coupled Purinergic Receptors Inhibit Insulin-like Growth Factor-I/Phosphoinositide 3-Kinase Pathway-dependent Keratinocyte Migration

2010 ◽  
Vol 21 (6) ◽  
pp. 946-955 ◽  
Author(s):  
Salma Taboubi ◽  
Françoise Garrouste ◽  
Fabrice Parat ◽  
Gilbert Pommier ◽  
Emilie Faure ◽  
...  
Keyword(s):  
Growth Factor ◽  
Purinergic Receptors ◽  
Purinergic Signaling ◽  
Extracellular Nucleotides ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Keratinocyte Migration ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor-I (IGF-I) activation of phosphoinositol 3-kinase (PI3K) is an essential pathway for keratinocyte migration that is required for epidermis wound healing. We have previously reported that activation of Gα(q/11)-coupled-P2Y2purinergic receptors by extracellular nucleotides delays keratinocyte wound closure. Here, we report that activation of P2Y2receptors by extracellular UTP inhibits the IGF-I–induced p110α-PI3K activation. Using siRNA and pharmacological inhibitors, we demonstrate that the UTP antagonistic effects on PI3K pathway are mediated by Gα(q/11)—and not G(i/o)—independently of phospholipase Cβ. Purinergic signaling does not affect the formation of the IGF-I receptor/insulin receptor substrate-I/p85 complex, but blocks the activity of a membrane-targeted active p110α mutant, indicating that UTP acts downstream of PI3K membrane recruitment. UTP was also found to efficiently attenuate, within few minutes, the IGF-I–induced PI3K-controlled translocation of the actin-nucleating protein cortactin to the plasma membrane. This supports the UTP ability to alter later migratory events. Indeed, UTP inhibits keratinocyte spreading and migration promoted by either IGF-I or a membrane-targeted active p110α mutant, in a Gα(q/11)-dependent manner both. These findings provide new insight into the signaling cross-talk between receptor tyrosine kinase and Gα(q/11)-coupled receptors, which mediate opposite effects on p110α-PI3K activity and keratinocyte migration.

scholarly journals Insulin-Like Growth Factor I Modifies Electrophysiological Properties of Rat Brain Stem Neurons

2003 ◽  
Vol 89 (6) ◽  
pp. 3008-3017 ◽  
Author(s):  
Angel Nuñez ◽  
Eva Carro ◽  
Ignacio Torres-Aleman
Keyword(s):  
Growth Factor ◽  
Brain Stem ◽  
Dorsal Column ◽  
Excitatory Postsynaptic Potential ◽  
Insulin Like Growth Factor ◽  
Electrophysiological Properties ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
The Brain

On systemic injection, insulin-like growth factor I (IGF-I) elicits a prolonged increase in the excitability of dorsal column nuclei (DCN) cells in the brain stem as well as other target neurons within the brain. We have explored the cellular mechanisms involved in the stimulatory effects of IGF-I as well as its functional consequences. In a rat slice preparation, IGF-I induced a sustained depolarization of 2–5 mV in 81% of DCN neurons. Depolarization was accompanied with an increase in the input resistance (15%). Voltage-clamp recordings displayed that IGF-I decreased a K+-mediated A current (60%). Furthermore, IGF-I increased, in 78% of cells, the peak amplitude (25%), and rising slope (32%) of the excitatory postsynaptic potential evoked by dorsal column stimulation; in this case, a presynaptic facilitatory process appears to be involved. When anesthetized adult rats are injected in the carotid artery with IGF-I, extracellularly recorded propioceptive DCN neurons not only show increased spike activity but also an expansion of their cutaneous receptive field in 83% of DCN cells. Significantly, the increased excitability evoked by IGF-I in the DCN cells depends both in vivo and in vitro, on activation of p38 mitogen-activated protein kinase (MAPK), a Ser-kinase known to modulate K+ channel activity. We concluded that systemic IGF-I modulated the electrophysiological properties of target neurons within the brain. In turn, these changes probably contribute to functional reorganization processes such as expansion of neuronal receptive fields.

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