In this episode of The Metabolic Classroom, Dr. Ben Bikman explores the metabolic effects of estrogens, particularly their role in glucose metabolism.
Estrogens, mainly produced in the gonads, play a crucial role in regulating blood glucose by enhancing insulin sensitivity. Dr. Bikman explained that estrogens improve insulin signaling through pathways such as PI3 kinase and AKT, which are essential for glucose uptake in muscle and fat tissues. Additionally, estrogens activate AMP-activated protein kinase (AMPK), further promoting glucose uptake and maintaining healthy blood glucose levels.
Estrogens also suppress glucose production in the liver by inhibiting key enzymes involved in gluconeogenesis, helping to prevent excess glucose release into the bloodstream. In contrast, progesterone decreases insulin sensitivity and promotes insulin resistance, counteracting some of estrogen's beneficial effects. This hormonal interplay affects glucose metabolism during the ovarian cycle, with estrogen-dominant phases being more favorable for glucose control.
During menopause, the significant drop in estrogen levels leads to increased insulin resistance and shifts in fat storage, often resulting in more central fat accumulation. While hormone replacement therapy (HRT) can mitigate some of these changes, it comes with risks that need careful consideration. Ben emphasizes the significant role of estrogens in glucose metabolism and their broader impact on metabolic health, especially in women.
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01:19 - Overview of Estrogens and Progesterone
02:20 - Cholesterol as the Precursor to Sex Hormones
03:34 - The Role of Aromatase in Estrogen Production
04:32 - Understanding the Family of Estrogens
05:56 - Estrogens and Glucose Metabolism: Key Signaling Pathways
06:54 - Insulin Signaling Pathway Overview
08:57 - How Estrogens Enhance Insulin Sensitivity
10:04 - The Role of AMPK in Glucose Uptake
12:11 - Estrogens' Dual Mechanism in Regulating Glucose Levels
13:18 - The Impact of Estrogens on Liver Glucose Production
15:33 - Estrogens' Role in Suppressing Gluconeogenesis
17:07 - Why Women Have Lower Risk of Type 2 Diabetes
19:28 - Metabolic Effects During the Ovarian Cycle
21:54 - Progesterone’s Influence on Insulin Resistance and Fat Storage
25:16 - The Shift in Fat Storage Patterns Post-Menopause
26:16 - Hormone Replacement Therapy: Metabolic Considerations
PI3K activation leads to the phosphorylation of Akt, a key protein in glucose metabolism, which promotes the translocation of GLUT4 (glucose transporter type 4) to the cell membrane, facilitating glucose uptake into muscle and adipose tissue: https://www.sciencedirect.com/science/article/pii/S155041311930138X?via%3Dihub
AMPK acts as an energy sensor and helps maintain cellular energy balance, which is crucial in regulating glucose and lipid metabolism: https://link.springer.com/article/10.1007/s12013-015-0521-z
Progesterone increases blood glucose levels by enhancing hepatic gluconeogenesis. This effect is mediated by the progesterone receptor membrane component 1 (PGRMC1) in the liver, which activates gluconeogenesis pathways, leading to increased glucose production, especially under conditions of insulin resistance: https://www.nature.com/articles/s41598-020-73330-7
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