Targeting Mitochondria in Diabetes

• Published in: International 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
• Language: English
• 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
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22126642

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.