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Artikel: Bio-Hacking Better Health-Leveraging Metabolic Biochemistry to Maximise Healthspan.

Cooper, Isabella D / Kyriakidou, Yvoni / Petagine, Lucy / Edwards, Kurtis / Elliott, Bradley T

2023 Band 12, Heft 9

Abstract: In the pursuit of longevity and healthspan, we are challenged with first overcoming chronic diseases of ageing: cardiovascular disease, hypertension, cancer, dementias, type 2 diabetes mellitus. These are hyperinsulinaemia diseases presented in different ...

Abstract	In the pursuit of longevity and healthspan, we are challenged with first overcoming chronic diseases of ageing: cardiovascular disease, hypertension, cancer, dementias, type 2 diabetes mellitus. These are hyperinsulinaemia diseases presented in different tissue types. Hyperinsulinaemia reduces endogenous antioxidants, via increased consumption and reduced synthesis. Hyperinsulinaemia enforces glucose fuelling, consuming 4 NAD
Sprache	Englisch
Erscheinungsdatum	2023-09-11
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12091749
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas.

Cooper, Isabella D / Brookler, Kenneth H / Crofts, Catherine A P

Biomedicines

2021 Band 9, Heft 9

Abstract: ... of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte ... propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport ... Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis. Carbohydrate restriction ...

Abstract	Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility "hyperinsulinaemia-osteofragilitas" phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures. Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis. Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.
Sprache	Englisch
Erscheinungsdatum	2021-09-06
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9091165
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Rethinking Fragility Fractures in Type 2 Diabetes

Isabella D. Cooper / Kenneth H. Brookler / Catherine A. P. Crofts

Biomedicines, Vol 9, Iss 1165, p

The Link between Hyperinsulinaemia and Osteofragilitas

2021 Band 1165

Abstract	Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility “hyperinsulinaemia-osteofragilitas” phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures. Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis. Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.
Schlagwörter	hyperinsulinaemia ; beta hydroxybutyrate ; osteoporosis ; type 2 diabetes ; fragility fractures ; bone mineral density ; Biology (General) ; QH301-705.5
Sprache	Englisch
Erscheinungsdatum	2021-09-01T00:00:00Z
Verlag	MDPI AG
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Buch ; Online: Socio-Technical Innovation Bundles for Agri-Food Systems Transformation

Barrett, Christopher B. / Benton, Tim / Fanzo, Jessica / Herrero, Mario / Nelson, Rebecca J. / Bageant, Elizabeth / Buckler, Edward / Cooper, Karen / Culotta, Isabella / Fan, Shenggen / Gandhi, Rikin / James, Steven / Kahn, Mark / Lawson-Lartego, Laté / Liu, Jiali / Marshall, Quinn / Mason-D'Croz, Daniel / Mathys, Alexander / Mathys, Cynthia /

Mazariegos-Anastassiou, Veronica / Miller, Alesha / Misra, Kamakhya / Mude, Andrew / Shen, Jianbo / Sibanda, Lindiwe Majele

(Sustainable Development Goals Series)

2022

Serientitel	Sustainable Development Goals Series
Schlagwörter	Agricultural science ; Environmental economics ; Sustainability ; Socio-technical innovation ; Agri-food systems ; Land and water footprint of food ; Climate crisis ; Human agency ; Heterogeneity ; Spillover effects ; Natural environment ; Public health ; Social justice
Sprache	0\|e
Umfang	1 electronic resource (195 pages)
Verlag	Springer Nature
Erscheinungsort	Cham
Dokumenttyp	Buch ; Online
Anmerkung	English ; Open Access
HBZ-ID	HT021614775
ISBN	9783030888022 ; 3030888029
Datenquelle	ZB MED Katalog Medizin, Gesundheit, Ernährung, Umwelt, Agrar

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Buch ; Online: Socio-Technical Innovation Bundles for Agri-Food Systems Transformation

Mazariegos-Anastassiou, Veronica / Miller, Alesha / Misra, Kamakhya / Mude, Andrew / Shen, Jianbo / Sibanda, Lindiwe Majele

(Sustainable Development Goals Series)

2022

Verfasserangabe	by Christopher B. Barrett, Tim Benton, Jessica Fanzo, Mario Herrero, Rebecca J. Nelson, Elizabeth Bageant, Edward Buckler, Karen Cooper, Isabella Culotta, Shenggen Fan, Rikin Gandhi, Steven James, Mark Kahn, Laté Lawson-Lartego, Jiali Liu, Quinn Marshall, Daniel Mason-D'Croz, Alexander Mathys, Cynthia Mathys, Veronica Mazariegos-Anastassiou, Alesha Miller, Kamakhya Misra, Andrew Mude, Jianbo Shen, Lindiwe Majele Sibanda, Claire Song, Roy Steiner, Philip Thornton, Stephen Wood
Serientitel	Sustainable Development Goals Series
Schlagwörter	Agriculture—Economic aspects ; Power resources ; Environmental economics ; Sustainability
Thema/Rubrik (Code)	338.1
Sprache	Englisch
Umfang	1 Online-Ressource (XXXIX, 195 p. 79 illus., 75 illus. in color)
Ausgabenhinweis	1st ed. 2022
Verlag	Springer International Publishing ; Imprint: Palgrave Macmillan
Erscheinungsort	Cham
Dokumenttyp	Buch ; Online
HBZ-ID	HT021360653
ISBN	978-3-030-88802-2 ; 9783030888015 ; 9783030888039 ; 9783030888046 ; 3-030-88802-9 ; 3030888010 ; 3030888037 ; 3030888045
DOI	10.1007/978-3-030-88802-2
Datenquelle	ZB MED Katalog Medizin, Gesundheit, Ernährung, Umwelt, Agrar

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Artikel: Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm.

Cooper, Isabella D / Brookler, Kenneth H / Kyriakidou, Yvoni / Elliott, Bradley T / Crofts, Catherine A P

Biomedicines

2021 Band 9, Heft 7

Abstract: Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these ... ...

Abstract	Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin's primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.
Sprache	Englisch
Erscheinungsdatum	2021-07-09
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9070800
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Thyroid markers and body composition predict LDL-cholesterol change in lean healthy women on a ketogenic diet: experimental support for the lipid energy model.

Cooper, Isabella D / Sanchez-Pizarro, Claudio / Norwitz, Nicholas G / Feldman, David / Kyriakidou, Yvoni / Edwards, Kurtis / Petagine, Lucy / Elliot, Bradley T / Soto-Mota, Adrian

Frontiers in endocrinology

2023 Band 14, Seite(n) 1326768

Abstract: Introduction: There is a large heterogeneity in LDL-cholesterol change among individuals adopting ketogenic diets. Interestingly, lean metabolically healthy individuals seem to be particularly susceptible, with an inverse association between body mass ... ...

Abstract	Introduction: There is a large heterogeneity in LDL-cholesterol change among individuals adopting ketogenic diets. Interestingly, lean metabolically healthy individuals seem to be particularly susceptible, with an inverse association between body mass index and LDL-cholesterol change. The lipid energy model proposes that, in lean healthy individuals, carbohydrate restriction upregulates systemic lipid trafficking to meet energy demands. To test if anthropometric and energy metabolism markers predict LDL-cholesterol change during carbohydrate restriction. Methods: Ten lean, healthy, premenopausal women who habitually consumed a ketogenic diet for ≥6 months were engaged in a three-phase crossover study consisting of continued nutritional ketosis, suppression of ketosis with carbohydrate reintroduction, and return to nutritional ketosis. Each phase lasted 21 days. The predictive performance of all available relevant variables was evaluated with the linear mixed-effects models. Results: All body composition metrics, free T Discussion: Among lean, healthy women undergoing carbohydrate restriction, body composition and energy metabolism markers are major drivers of LDL-cholesterol change, not saturated fat, consistent with the lipid energy model.
Mesh-Begriff(e)	Humans ; Female ; Diet, Ketogenic ; Cross-Over Studies ; Thyroid Gland ; Body Composition ; Cholesterol, LDL ; Ketosis ; Carbohydrates
Chemische Substanzen	Cholesterol, LDL ; Carbohydrates
Sprache	Englisch
Erscheinungsdatum	2023-12-21
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1326768
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females.

Cooper, Isabella D / Kyriakidou, Yvoni / Edwards, Kurtis / Petagine, Lucy / Seyfried, Thomas N / Duraj, Tomas / Soto-Mota, Adrian / Scarborough, Andrew / Jacome, Sandra L / Brookler, Kenneth / Borgognoni, Valentina / Novaes, Vanusa / Al-Faour, Rima / Elliott, Bradley T

International journal of molecular sciences

2023 Band 24, Heft 21

Abstract: ... capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 pmol/L ...

Abstract	Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Adherence to each phase was confirmed with daily capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 pmol/L). Ageing biomarkers and anthropometrics were evaluated at the end of each phase. Ketosis suppression significantly increased: insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) pmol/L (
Mesh-Begriff(e)	Animals ; Cattle ; Humans ; Male ; Female ; Young Adult ; Adult ; Cattle Diseases/metabolism ; Ketosis ; Diet, Ketogenic ; Insulin/pharmacology ; Hyperinsulinism ; 3-Hydroxybutyric Acid/metabolism
Chemische Substanzen	Insulin ; 3-Hydroxybutyric Acid (TZP1275679)
Sprache	Englisch
Erscheinungsdatum	2023-10-26
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242115621
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes

Isabella D. Cooper / Kenneth H. Brookler / Yvoni Kyriakidou / Bradley T. Elliott / Catherine A. P. Crofts

Biomedicines, Vol 9, Iss 800, p

A New Paradigm

2021 Band 800

Abstract	Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin’s primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.
Schlagwörter	hyperinsulinaemia ; insulin resistance ; osteocalcin ; beta-hydroxybutyrate ; phenotype ; stages ; Biology (General) ; QH301-705.5
Thema/Rubrik (Code)	571
Sprache	Englisch
Erscheinungsdatum	2021-07-01T00:00:00Z
Verlag	MDPI AG
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Ketosis Suppression and Ageing (KetoSAge)

Isabella D. Cooper / Yvoni Kyriakidou / Kurtis Edwards / Lucy Petagine / Thomas N. Seyfried / Tomas Duraj / Adrian Soto-Mota / Andrew Scarborough / Sandra L. Jacome / Kenneth Brookler / Valentina Borgognoni / Vanusa Novaes / Rima Al-Faour / Bradley T. Elliott

International Journal of Molecular Sciences, Vol 24, Iss 21, p

The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females

2023 Band 15621

Abstract: ... capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 pmol/L ...

Abstract	Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Adherence to each phase was confirmed with daily capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 pmol/L). Ageing biomarkers and anthropometrics were evaluated at the end of each phase. Ketosis suppression significantly increased: insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) pmol/L ( p = 0.0002); IGF1, 1.83-fold from 149.30 (± 32.96) to 273.40 (± 85.66) µg/L ( p = 0.0045); glucose, 1.17-fold from 78.6 (± 9.5) to 92.2 (± 10.6) mg/dL ( p = 0.0088); respiratory quotient (RQ), 1.09-fold 0.66 (± 0.05) to 0.72 (± 0.06; p = 0.0427); and PAI-1, 13.34 (± 6.85) to 16.69 (± 6.26) ng/mL ( p = 0.0428). VEGF, EGF, and monocyte chemotactic protein also significantly increased, indicating a pro-inflammatory shift. Sustained ketosis showed no adverse health effects, and may mitigate hyperinsulinemia without impairing metabolic flexibility in metabolically healthy women.
Schlagwörter	ageing ; beta-hydroxybutyrate ; cancer ; hyperinsulinaemia ; insulin resistance ; ketosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Sprache	Englisch
Erscheinungsdatum	2023-10-01T00:00:00Z
Verlag	MDPI AG
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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