Targeting Mitochondria in Diabetes.
Nina Krako JakovljevicKasja PavlovicAleksandra JoticKatarina LalicMilica StoiljkovicLjiljana LukicTanja MilicicMarija MacesicJelena Stanarcic GajovicNebojsa M LalicPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- type diabetes
- insulin resistance
- glycemic control
- skeletal muscle
- cell death
- physical activity
- cardiovascular disease
- reactive oxygen species
- endoplasmic reticulum
- blood glucose
- cell cycle arrest
- metabolic syndrome
- endothelial cells
- gene expression
- induced apoptosis
- healthcare
- oxidative stress
- weight loss
- adipose tissue
- public health
- cancer therapy
- case control
- small molecule
- high fat diet
- high intensity
- machine learning
- resistance training
- big data
- body composition
- health information
- cell proliferation
- network analysis
- pluripotent stem cells
- health promotion