Type 2 diabetes (T2D) is characterized by a state of hyperglycemia in the blood due to insulin resistance developed by organs such as muscle, liver, and adipose tissue. A common factor in individuals with T2D is mitochondrial dysfunction. Mitochondria are dynamic organelles responsible for energy and antioxidant metabolism in the cells. Estrogens, such as 17β-estradiol (E2), are steroid hormones that have shown a great capacity to regulate mitochondrial function and dynamics through estrogen receptors (ERs), modulating the expression of mitochondrial biogenesis-related genes and cell signaling mechanisms. The accumulation of reactive oxygen species, the low capacity for ATP synthesis, and morphological alterations are some of the mitochondrial processes impaired in T2D. Insulin signaling and secretion by pancreatic β-cells, ATP-dependent processes, are also altered in T2D. In this review, mitochondria were exposed as the central axis for the action of estrogens in individuals with T2D. Estrogens increased glucose uptake, insulin signaling, and mitochondrial bioenergetics, and decreased ectopic lipid accumulation in non-adipose tissues and oxidative stress, among other processes, in various preclinical and clinical models of diabetes. The development of strategies to target compounds to mitochondria could represent a novel therapeutic alternative to potentiate the effects of estrogens on this organelle in patients with insulin resistance and T2D.
Citation: Geovanni Alberto Ruiz-Romero, Carolina Álvarez-Delgado. Effects of estrogens in mitochondria: An approach to type 2 diabetes[J]. AIMS Molecular Science, 2024, 11(1): 72-98. doi: 10.3934/molsci.2024006
Type 2 diabetes (T2D) is characterized by a state of hyperglycemia in the blood due to insulin resistance developed by organs such as muscle, liver, and adipose tissue. A common factor in individuals with T2D is mitochondrial dysfunction. Mitochondria are dynamic organelles responsible for energy and antioxidant metabolism in the cells. Estrogens, such as 17β-estradiol (E2), are steroid hormones that have shown a great capacity to regulate mitochondrial function and dynamics through estrogen receptors (ERs), modulating the expression of mitochondrial biogenesis-related genes and cell signaling mechanisms. The accumulation of reactive oxygen species, the low capacity for ATP synthesis, and morphological alterations are some of the mitochondrial processes impaired in T2D. Insulin signaling and secretion by pancreatic β-cells, ATP-dependent processes, are also altered in T2D. In this review, mitochondria were exposed as the central axis for the action of estrogens in individuals with T2D. Estrogens increased glucose uptake, insulin signaling, and mitochondrial bioenergetics, and decreased ectopic lipid accumulation in non-adipose tissues and oxidative stress, among other processes, in various preclinical and clinical models of diabetes. The development of strategies to target compounds to mitochondria could represent a novel therapeutic alternative to potentiate the effects of estrogens on this organelle in patients with insulin resistance and T2D.
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Figures(2)
Geovanni Alberto Ruiz-Romero, Carolina Álvarez-Delgado. Effects of estrogens in mitochondria: An approach to type 2 diabetes[J]. AIMS Molecular Science, 2024, 11(1): 72-98. doi: 10.3934/molsci.2024006
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