Targeting Mitochondria in Diabetes

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, a...

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Published inInternational journal of molecular sciences Vol. 22; no. 12; p. 6642
Main Authors Krako Jakovljevic, Nina, Pavlovic, Kasja, Jotic, Aleksandra, Lalic, Katarina, Stoiljkovic, Milica, Lukic, Ljiljana, Milicic, Tanja, Macesic, Marija, Stanarcic Gajovic, Jelena, Lalic, Nebojsa M.
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 21.06.2021
MDPI
Subjects
Adenosine triphosphate
Animals
Biopsy
Biosynthesis
Diabetes
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Disease
Enzymes
Exercise
Fatty acids
Glucose
Homeostasis
Human subjects
Humans
Hyperglycemia
Hypoglycemic Agents - pharmacology
Hypoglycemic Agents - therapeutic use
Hypotheses
Insulin resistance
Liver
Metabolism
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondrial DNA
Musculoskeletal system
Nervous system
Pancreas
Pathogenesis
Phosphorylation
Physical fitness
Respiration
Review
diabetes therapy
type 2 diabetes
liver
mitochondria
blood cells
exercise
respiration
skeletal muscle
insulin resistance
respiratory capacity
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Abstract Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.
AbstractList Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.
Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.
Author Lalic, Katarina
Stoiljkovic, Milica
Stanarcic Gajovic, Jelena
Jotic, Aleksandra
Macesic, Marija
Lukic, Ljiljana
Milicic, Tanja
Krako Jakovljevic, Nina
Lalic, Nebojsa M.
Pavlovic, Kasja
AuthorAffiliation Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia; nina.krako@med.bg.ac.rs (N.K.J.); kasja.pavlovic@med.bg.ac.rs (K.P.); aleksandra.z.jotic@gmail.com (A.J.); katarina.s.lalic@gmail.com (K.L.); mmstoiljkovic@yahoo.com (M.S.); ljikson17@gmail.com (L.L.); icataca@gmail.com (T.M.); macesicmarija@gmail.com (M.M.); stanarcicjelena@gmail.com (J.S.G.)
AuthorAffiliation_xml – name: Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia; nina.krako@med.bg.ac.rs (N.K.J.); kasja.pavlovic@med.bg.ac.rs (K.P.); aleksandra.z.jotic@gmail.com (A.J.); katarina.s.lalic@gmail.com (K.L.); mmstoiljkovic@yahoo.com (M.S.); ljikson17@gmail.com (L.L.); icataca@gmail.com (T.M.); macesicmarija@gmail.com (M.M.); stanarcicjelena@gmail.com (J.S.G.)
Author_xml – sequence: 1
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  orcidid: 0000-0003-3908-5462
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  surname: Stanarcic Gajovic
  fullname: Stanarcic Gajovic, Jelena
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  givenname: Nebojsa M.
  surname: Lalic
  fullname: Lalic, Nebojsa M.
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Keywords diabetes therapy
type 2 diabetes
liver
mitochondria
blood cells
exercise
respiration
skeletal muscle
insulin resistance
respiratory capacity
Language English
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Snippet Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of...
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SubjectTerms Adenosine triphosphate
Animals
Biopsy
Biosynthesis
Diabetes
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Disease
Enzymes
Exercise
Fatty acids
Glucose
Homeostasis
Human subjects
Humans
Hyperglycemia
Hypoglycemic Agents - pharmacology
Hypoglycemic Agents - therapeutic use
Hypotheses
Insulin resistance
Liver
Metabolism
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondrial DNA
Musculoskeletal system
Nervous system
Pancreas
Pathogenesis
Phosphorylation
Physical fitness
Respiration
Review
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Title Targeting Mitochondria in Diabetes
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