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Article: The Insulin Receptor Mediates Insulin's Early Plasma Clearance by Liver, Muscle, and Kidney.

Meijer, Rick I / Barrett, Eugene J

2021 Volume 9, Issue 1

Abstract: The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([ ...

Abstract	The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([
Language	English
Publishing date	2021-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9010037
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney

Rick I. Meijer / Eugene J. Barrett

Biomedicines, Vol 9, Iss 37, p

2021 Volume 37

Abstract	The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([ 125 I]Tyr A14 )-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([ 125 I]Tyr A14 )insulin concentration approximately 5-fold ( p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle ( p < 0.01), liver ( p < 0.05), and kidney ( p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance ( p = 0.056) while increasing renal clearance by >50% ( p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.
Keywords	insulin clearance ; insulin receptor ; muscle ; liver ; kidney ; S961 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Disease Duration and Chronic Complications Associate With Immune Activation in Individuals With Longstanding Type 1 Diabetes.

Ajie, Mandala / van Heck, Julia I P / Janssen, Anna W M / Meijer, Rick I / Tack, Cees J / Stienstra, Rinke

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 8, Page(s) 1909–1920

Abstract: Context: Type 1 diabetes (T1D) is associated with alterations of the immune response which persist even after the autoimmunity aspect is resolved. Clinical factors that cause dysregulation, however, are not fully understood.: Objective: To identify ... ...

Abstract	Context: Type 1 diabetes (T1D) is associated with alterations of the immune response which persist even after the autoimmunity aspect is resolved. Clinical factors that cause dysregulation, however, are not fully understood. Objective: To identify clinical factors that affect immune dysregulation in people with longstanding T1D. Design: In this cross-sectional study, 243 participants with longstanding T1D were recruited between February 2016 and June 2017 at the Radboudumc, the Netherlands. Blood was drawn to determine immune cell phenotype and functionality, as well as circulating inflammatory proteome. Multivariate linear regression was used to determine the association between glycated hemoglobin (HbA1c) levels, duration of diabetes, insulin need, and diabetes complications with inflammation. Results: HbA1c level is positively associated with circulating inflammatory markers (P < .05), but not with immune cell number and phenotype. Diabetes duration is associated with increased number of circulating immune cells (P < .05), inflammatory proteome (P < .05), and negatively associated with adaptive immune response against Mycobacterium tuberculosis and Rhizopus oryzae (P < .05). Diabetes nephropathy is associated with increased circulating immune cells (P < .05) and inflammatory markers (P < .05). Conclusion: Disease duration and chronic complications associate with persistent alterations in the immune response of individuals with long standing T1D.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/complications ; Glycated Hemoglobin ; Cross-Sectional Studies ; Proteome ; Diabetes Complications
Chemical Substances	Glycated Hemoglobin ; Proteome
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad087
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Article ; Online: Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study.

Hennis, Philip J / Murphy, Elaine / Meijer, Rick I / Lachmann, Robin H / Ramachandran, Radha / Bordoli, Claire / Rayat, Gurinder / Tomlinson, David J

Orphanet journal of rare diseases

2022 Volume 17, Issue 1, Page(s) 28

Abstract: Background: Individuals with glycogen storage disease IIIa (GSD IIIa) (OMIM #232400) experience muscle weakness and exercise limitation that worsen through adulthood. However, normative data for markers of physical capacity, such as strength and ... ...

Abstract	Background: Individuals with glycogen storage disease IIIa (GSD IIIa) (OMIM #232400) experience muscle weakness and exercise limitation that worsen through adulthood. However, normative data for markers of physical capacity, such as strength and cardiovascular fitness, are limited. Furthermore, the impact of the disease on muscle size and quality is unstudied in weight bearing skeletal muscle, a key predictor of physical function. We aim to produce normative reference values of aerobic capacity and strength in individuals with GSD IIIa, and to investigate the role of muscle size and quality on exercise impairment. Results: Peak oxygen uptake (V̇O Conclusions: V̇O
MeSH term(s)	Adult ; Exercise/physiology ; Glycogen Storage Disease Type III ; Humans ; Muscle Strength/physiology ; Muscle, Skeletal ; Quality of Life
Language	English
Publishing date	2022-01-31
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2225857-7
ISSN	1750-1172 ; 1750-1172
ISSN (online)	1750-1172
ISSN	1750-1172
DOI	10.1186/s13023-022-02184-1
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Book ; Online: Supplementary table 1-6

Ajie, Mandala / van Heck, Julia I.P. / M. Jansen, Anna / Meijer, Rick / Tack, Cees J. / Stienstra, Rinke

2023

Abstract: Supplementary tables 1-6. Details on the statistical analyses performed on the relation between diabetes duration, insulin need, HbA1c levels, and diabetes complications with circulating immune cells (Supp table 1 & 2), PBMCs ex vivo stimulation (Supp ... ...

Abstract	Supplementary tables 1-6. Details on the statistical analyses performed on the relation between diabetes duration, insulin need, HbA1c levels, and diabetes complications with circulating immune cells (Supp table 1 & 2), PBMCs ex vivo stimulation (Supp table 3 & 4), and circulating inflammatory proteome (Supp table 5 & 6)
Keywords	diabetes and endocrine research ; inflammation
Publisher	Radboud Universiteit
Publishing country	nl
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Disease Duration and Chronic Complications Associate With Immune Activation in Individuals With Longstanding Type 1 Diabetes

Ajie, Mandala / van Heck, Julia I.P. / Janssen, Anna W.M. / Meijer, Rick I. / Tack, Cees J. / Stienstra, Rinke

Journal of Clinical Endocrinology and Metabolism

2023 Volume 108, Issue 8

Abstract: ContextType 1 diabetes (T1D) is associated with alterations of the immune response which persist even after the autoimmunity aspect is resolved. Clinical factors that cause dysregulation, however, are not fully understood.ObjectiveTo identify clinical ... ...

Abstract	ContextType 1 diabetes (T1D) is associated with alterations of the immune response which persist even after the autoimmunity aspect is resolved. Clinical factors that cause dysregulation, however, are not fully understood.ObjectiveTo identify clinical factors that affect immune dysregulation in people with longstanding T1D.DesignIn this cross-sectional study, 243 participants with longstanding T1D were recruited between February 2016 and June 2017 at the Radboudumc, the Netherlands. Blood was drawn to determine immune cell phenotype and functionality, as well as circulating inflammatory proteome. Multivariate linear regression was used to determine the association between glycated hemoglobin (HbA1c) levels, duration of diabetes, insulin need, and diabetes complications with inflammation.ResultsHbA1c level is positively associated with circulating inflammatory markers (P < .05), but not with immune cell number and phenotype. Diabetes duration is associated with increased number of circulating immune cells (P < .05), inflammatory proteome (P < .05), and negatively associated with adaptive immune response against Mycobacterium tuberculosis and Rhizopus oryzae (P < .05). Diabetes nephropathy is associated with increased circulating immune cells (P < .05) and inflammatory markers (P < .05)ConclusionDisease duration and chronic complications associate with persistent alterations in the immune response of individuals with long standing T1D.
Keywords	Life Science
Subject code	616
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Charge transport modulation by a redox supramolecular spin-filtering chiral crystal

Verhage, Michael / Bampoulis, Pantelis / Preuss, Marco D. / Filot, Ivo / Friedrich, Heiner / Joosten, Rick R. M. / Meijer, E. W. / Flipse, Kees

2023

Abstract: The chirality induced spin selectivity (CISS) effect is a fascinating phenomena correlating molecular structure with electron spin-polarisation in excited state measurements. Experimental procedures to quantify the spin-filtering magnitude relies ... ...

Abstract	The chirality induced spin selectivity (CISS) effect is a fascinating phenomena correlating molecular structure with electron spin-polarisation in excited state measurements. Experimental procedures to quantify the spin-filtering magnitude relies generally on averaging data sets, especially those from magnetic field dependent conductive-AFM. We investigate the underlying observed disorder in the IV spectra and the origin of spikes superimposed. We demonstrate and explain that a dynamic, voltage sweep rate dependent, phenomena can give rise to complex IV curves for chiral crystals of coronene bisimide. The redox group, able to capture localized charge states, acts as an impurity state interfering with a continuum, giving rise to Fano resonances. We introduce a novel mechanism for the dynamic transport which might also provide insight into the role of spin-polarization. Crucially, interference between charge localisation and delocalisation during transport may be important properties into understanding the CISS phenomena.
Keywords	Condensed Matter - Materials Science ; Condensed Matter - Mesoscale and Nanoscale Physics
Subject code	530
Publishing date	2023-04-09
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa

Philip J. Hennis / Elaine Murphy / Rick I. Meijer / Robin H. Lachmann / Radha Ramachandran / Claire Bordoli / Gurinder Rayat / David J. Tomlinson

Orphanet Journal of Rare Diseases, Vol 17, Iss 1, Pp 1-

an observational study

2022 Volume 12

Abstract: Abstract Background Individuals with glycogen storage disease IIIa (GSD IIIa) (OMIM #232400) experience muscle weakness and exercise limitation that worsen through adulthood. However, normative data for markers of physical capacity, such as strength and ... ...

Abstract	Abstract Background Individuals with glycogen storage disease IIIa (GSD IIIa) (OMIM #232400) experience muscle weakness and exercise limitation that worsen through adulthood. However, normative data for markers of physical capacity, such as strength and cardiovascular fitness, are limited. Furthermore, the impact of the disease on muscle size and quality is unstudied in weight bearing skeletal muscle, a key predictor of physical function. We aim to produce normative reference values of aerobic capacity and strength in individuals with GSD IIIa, and to investigate the role of muscle size and quality on exercise impairment. Results Peak oxygen uptake (V̇O2peak) was lower in the individuals with GSD IIIa than predicted based on demographic data (17.0 (9.0) ml/kg/min, 53 (24)% of predicted, p = 0.001). Knee extension maximum voluntary contraction (MVC) was also substantially lower than age matched predicted values (MVC: 146 (116) Nm, 57% predicted, p = 0.045), though no difference was found in MVC relative to body mass (1.88 (2.74) Nm/kg, 61% of predicted, p = 0.263). There was a strong association between aerobic capacity and maximal leg strength (r = 0.920; p = 0.003). Substantial inter-individual variation was present, with a high physical capacity group that had normal leg strength (MVC), and relatively high V̇O2peak, and a low physical capacity that display impaired strength and substantially lower V̇O2peak. The higher physical capacity sub-group were younger, had larger Vastus Lateralis (VL) muscles, greater muscle quality, undertook more physical activity (PA), and reported higher health-related quality of life. Conclusions V̇O2peak and knee extension strength are lower in individuals with GSD IIIa than predicted based on their demographic data. Patients with higher physical capacity have superior muscle size and structure characteristics and higher health-related quality of life, than those with lower physical capacity. This study provides normative values of these important markers of physical capacity.
Keywords	Skeletal muscle ; Glycogen storage disease type IIIa ; Maximum voluntary contraction ; Aerobic capacity ; Medicine ; R
Subject code	796
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Titrating Growth Hormone Dose to High-Normal IGF-1 Levels Has Beneficial Effects on Body Fat Distribution and Microcirculatory Function Despite Causing Insulin Resistance.

van Bunderen, Christa C / Meijer, Rick I / Lips, Paul / Kramer, Mark H / Serné, Erik H / Drent, Madeleine L

Frontiers in endocrinology

2021 Volume 11, Page(s) 619173

Abstract: To clarify the mechanism underlying the described U-shaped relation of both low and high levels of IGF-1 with cardiovascular disease this study explores the effect of decreasing and increasing growth hormone dose in GH deficient adults on (micro)vascular ...

Abstract	To clarify the mechanism underlying the described U-shaped relation of both low and high levels of IGF-1 with cardiovascular disease this study explores the effect of decreasing and increasing growth hormone dose in GH deficient adults on (micro)vascular function, body composition and insulin resistance. In this randomized clinical trial, thirty-two subjects receiving GH therapy with an IGF-1 concentration between -1 and 1 SD score (SDS) for at least one year were randomized to receive either a decrease (IGF-1 target level of -2 to -1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Microvascular endothelium (in)dependent vasodilatation and vasomotion, vascular stiffness by pulse wave analysis, and HOMA-IR were measured. At the end of the study 30 subjects (65.6% men, mean age 46.6 (SD 9.9) years) were analyzed. There was a favorable effect of increasing the IGF-1 level on waist circumference compared to decreasing the IGF-1 level (p=0.05), but a detrimental effect on insulin resistance (p=0.03). Decreasing IGF-1 level significantly lowered the endothelial domain of vasomotion (p=0.03), whereas increasing IGF-1 level increased the contribution of the neurogenic domain (p=0.05). This change was related to the favorable change in waist circumference. In conclusion, increasing IGF-1 levels was beneficial for body composition but detrimental with respect to insulin resistance. The contribution of the neurogenic vasomotion domain increased in parallel, and could be explained by the favorable change in waist circumference. Clinical trial registration: ClinicalTrials.gov, identifier NCT01877512.
MeSH term(s)	Adult ; Body Composition/drug effects ; Body Composition/physiology ; Body Fat Distribution/methods ; Dose-Response Relationship, Drug ; Female ; Human Growth Hormone/administration & dosage ; Human Growth Hormone/deficiency ; Humans ; Insulin Resistance/physiology ; Insulin-Like Growth Factor I/metabolism ; Male ; Microcirculation/physiology ; Middle Aged ; Waist Circumference/drug effects ; Waist Circumference/physiology
Chemical Substances	IGF1 protein, human ; Human Growth Hormone (12629-01-5) ; Insulin-Like Growth Factor I (67763-96-6)
Language	English
Publishing date	2021-02-09
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2020.619173
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pathways for insulin access to the brain: the role of the microvascular endothelial cell.

Meijer, Rick I / Gray, Sarah M / Aylor, Kevin W / Barrett, Eugene J

American journal of physiology. Heart and circulatory physiology

2016 Volume 311, Issue 5, Page(s) H1132–H1138

Abstract: Insulin affects multiple important central nervous system (CNS) functions including memory and appetite, yet the pathway(s) by which insulin reaches brain interstitial fluid (bISF) has not been clarified. Recent studies demonstrate that to reach bISF, ... ...

Abstract	Insulin affects multiple important central nervous system (CNS) functions including memory and appetite, yet the pathway(s) by which insulin reaches brain interstitial fluid (bISF) has not been clarified. Recent studies demonstrate that to reach bISF, subarachnoid cerebrospinal fluid (CSF) courses through the Virchow-Robin space (VRS) which sheaths penetrating pial vessels down to the capillary level. Whether insulin predominantly enters the VRS and bISF by local transport through the blood-brain barrier, or by being secreted into the CSF by the choroid plexus, is unknown. We injected
MeSH term(s)	Animals ; Biological Transport ; Blood-Brain Barrier/metabolism ; Cerebrospinal Fluid/metabolism ; Diet, High-Fat ; Endothelial Cells/metabolism ; Enzyme-Linked Immunosorbent Assay ; Extracellular Fluid/metabolism ; Glucose Clamp Technique ; Hypoglycemic Agents/pharmacokinetics ; In Vitro Techniques ; Injections, Intravenous ; Injections, Intraventricular ; Insulin/pharmacokinetics ; Iodine Radioisotopes ; Male ; Microvessels/metabolism ; Pia Mater/blood supply ; Rats ; Rats, Sprague-Dawley ; Receptor, Insulin/antagonists & inhibitors ; Receptor, Insulin/metabolism ; Subarachnoid Space/metabolism
Chemical Substances	Hypoglycemic Agents ; Insulin ; Iodine Radioisotopes ; Receptor, Insulin (EC 2.7.10.1)
Language	English
Publishing date	2016-09-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00081.2016
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