Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease

Sanjay Kalra,1,2 Ambika Gopalakrishnan Unnikrishnan,3 Manash P Baruah,4 Rakesh Sahay,5 Ganapathi Bantwal6 1Department of Endocrinology, Bharti Hospital, Karnal, India; 2Department of Endocrinology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India; 3Department of Endocrinology a...

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Autores principales:	Kalra S, Unnikrishnan AG, Baruah MP, Sahay R, Bantwal G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	metabolic flexibility dbcd insulin resistance prediabetes diabetes microvascular and macrovascular complication. Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/7a86714964f140a3a6a3f5bae17a51f9
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spelling	oai:doaj.org-article:7a86714964f140a3a6a3f5bae17a51f92021-12-02T14:12:12ZMetabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease1178-7007https://doaj.org/article/7a86714964f140a3a6a3f5bae17a51f92021-01-01T00:00:00Zhttps://www.dovepress.com/metabolic-and-energy-imbalance-in-dysglycemia-based-chronic-disease-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Sanjay Kalra,1,2 Ambika Gopalakrishnan Unnikrishnan,3 Manash P Baruah,4 Rakesh Sahay,5 Ganapathi Bantwal6 1Department of Endocrinology, Bharti Hospital, Karnal, India; 2Department of Endocrinology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India; 3Department of Endocrinology and Diabetes, Chellaram Diabetes Institute, Pune, Maharashtra, India; 4Department of Endocrinology, Excel Hospitals, Guwahati, India; 5Department of Endocrinology, Osmania Medical College, Hyderabad, Telangana, India; 6Department of Endocrinology, St. John’s Medical College and Hospital, Bangalore, Karnataka, IndiaCorrespondence: Sanjay KalraBharti Hospital, Kunjpura Road, Karnal, 132001 Haryana, IndiaTel +919896048555Email brideknl@gmail.comAbstract: Metabolic flexibility is the ability to efficiently adapt metabolism based on nutrient availability and requirement that is essential to maintain homeostasis in times of either caloric excess or restriction and during the energy-demanding state. This regulation is orchestrated in multiple organ systems by the alliance of numerous metabolic pathways under the master control of the insulin-glucagon-sympathetic neuro-endocrine axis. This, in turn, regulates key metabolic enzymes and transcription factors, many of which interact closely with and culminate in the mitochondrial energy generation machinery. Metabolic flexibility is compromised due to the continuous mismatch between availability and intake of calorie-dense foods and reduced metabolic demand due to sedentary lifestyle and age-related metabolic slowdown. The resultant nutrient overload leads to mitochondrial trafficking of substrates manifesting as mitochondrial dysfunction characterized by ineffective substrate switching and incomplete substrate utilization. At the systemic level, the manifestation of metabolic inflexibility comprises reduced skeletal muscle glucose disposal rate, impaired suppression of hepatic gluconeogenesis and adipose tissue lipolysis manifesting as insulin resistance. This is compounded by impaired β-cell function and progressively reduced β-cell mass. A consequence of insulin resistance is the upregulation of the mitogen-activated protein kinase pathway leading to a pro-hypertensive, atherogenic, and thrombogenic environment. This is further aggravated by oxidative stress, advanced glycation end products, and inflammation, which potentiates the risk of micro- and macro-vascular complications. This review aims to elucidate underlying mechanisms mediating the onset of metabolic inflexibility operating at the main target organs and to understand the progression of metabolic diseases. This could potentially translate into a pharmacological tool that can manage multiple interlinked conditions of dysglycemia, hypertension, and dyslipidemia by restoring metabolic flexibility. We discuss the breadth and depth of metabolic flexibility and its impact on health and disease.Keywords: metabolic flexibility, DBCD, insulin resistance, prediabetes, diabetes, microvascular and macrovascular complicationKalra SUnnikrishnan AGBaruah MPSahay RBantwal GDove Medical Pressarticlemetabolic flexibilitydbcdinsulin resistanceprediabetesdiabetesmicrovascular and macrovascular complication.Specialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 165-184 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	metabolic flexibility dbcd insulin resistance prediabetes diabetes microvascular and macrovascular complication. Specialties of internal medicine RC581-951
spellingShingle	metabolic flexibility dbcd insulin resistance prediabetes diabetes microvascular and macrovascular complication. Specialties of internal medicine RC581-951 Kalra S Unnikrishnan AG Baruah MP Sahay R Bantwal G Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease
description	Sanjay Kalra,1,2 Ambika Gopalakrishnan Unnikrishnan,3 Manash P Baruah,4 Rakesh Sahay,5 Ganapathi Bantwal6 1Department of Endocrinology, Bharti Hospital, Karnal, India; 2Department of Endocrinology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India; 3Department of Endocrinology and Diabetes, Chellaram Diabetes Institute, Pune, Maharashtra, India; 4Department of Endocrinology, Excel Hospitals, Guwahati, India; 5Department of Endocrinology, Osmania Medical College, Hyderabad, Telangana, India; 6Department of Endocrinology, St. John’s Medical College and Hospital, Bangalore, Karnataka, IndiaCorrespondence: Sanjay KalraBharti Hospital, Kunjpura Road, Karnal, 132001 Haryana, IndiaTel +919896048555Email brideknl@gmail.comAbstract: Metabolic flexibility is the ability to efficiently adapt metabolism based on nutrient availability and requirement that is essential to maintain homeostasis in times of either caloric excess or restriction and during the energy-demanding state. This regulation is orchestrated in multiple organ systems by the alliance of numerous metabolic pathways under the master control of the insulin-glucagon-sympathetic neuro-endocrine axis. This, in turn, regulates key metabolic enzymes and transcription factors, many of which interact closely with and culminate in the mitochondrial energy generation machinery. Metabolic flexibility is compromised due to the continuous mismatch between availability and intake of calorie-dense foods and reduced metabolic demand due to sedentary lifestyle and age-related metabolic slowdown. The resultant nutrient overload leads to mitochondrial trafficking of substrates manifesting as mitochondrial dysfunction characterized by ineffective substrate switching and incomplete substrate utilization. At the systemic level, the manifestation of metabolic inflexibility comprises reduced skeletal muscle glucose disposal rate, impaired suppression of hepatic gluconeogenesis and adipose tissue lipolysis manifesting as insulin resistance. This is compounded by impaired β-cell function and progressively reduced β-cell mass. A consequence of insulin resistance is the upregulation of the mitogen-activated protein kinase pathway leading to a pro-hypertensive, atherogenic, and thrombogenic environment. This is further aggravated by oxidative stress, advanced glycation end products, and inflammation, which potentiates the risk of micro- and macro-vascular complications. This review aims to elucidate underlying mechanisms mediating the onset of metabolic inflexibility operating at the main target organs and to understand the progression of metabolic diseases. This could potentially translate into a pharmacological tool that can manage multiple interlinked conditions of dysglycemia, hypertension, and dyslipidemia by restoring metabolic flexibility. We discuss the breadth and depth of metabolic flexibility and its impact on health and disease.Keywords: metabolic flexibility, DBCD, insulin resistance, prediabetes, diabetes, microvascular and macrovascular complication
format	article
author	Kalra S Unnikrishnan AG Baruah MP Sahay R Bantwal G
author_facet	Kalra S Unnikrishnan AG Baruah MP Sahay R Bantwal G
author_sort	Kalra S
title	Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease
title_short	Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease
title_full	Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease
title_fullStr	Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease
title_full_unstemmed	Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease
title_sort	metabolic and energy imbalance in dysglycemia-based chronic disease
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/7a86714964f140a3a6a3f5bae17a51f9
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Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease

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