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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Dr. Ben Bikman, a biomedical scientist and professor of cell biology, discusses the phenomenon of anabolic resistance.

Anabolic resistance, primarily a problem associated with aging, refers to the reduced ability of muscles to synthesize protein in response to anabolic stimuli, such as protein intake and resistance exercise. This condition leads to a decline in muscle mass and function over time, contributing to a loss of physical capacity, increased risk of falls, and a greater dependency on others for daily living.

Dr. Bikman emphasizes the importance of muscle mass for overall health. Beyond physical function, muscle plays a crucial role in metabolic regulation, particularly glucose metabolism and insulin sensitivity. Muscle acts as a “glucose sink,” helping to regulate blood glucose levels and maintain insulin sensitivity. Therefore, maintaining muscle mass is vital for preventing metabolic disorders and enhancing longevity and health span.

Anabolic resistance is influenced by various age-related factors, including hormonal changes, reduced physical activity, insufficient protein intake, and chronic illnesses such as insulin resistance. The key intracellular signal involved in muscle protein synthesis is the mTOR1 pathway, which becomes less responsive with age and insulin resistance. Dr. Bikman also discusses the controversial use of rapamycin, a drug promoted by some longevity enthusiasts, which can inhibit mTOR1 and potentially exacerbate anabolic resistance and insulin resistance.

To combat anabolic resistance, Dr. Bikman highlights the importance of dietary and exercise interventions. Older adults require higher protein intake, particularly high-quality protein sources rich in leucine, to stimulate muscle protein synthesis effectively. Additionally, resistance exercise is crucial, with a focus on going to muscle fatigue to promote maximal muscle protein synthesis. Dr. Bikman stresses the need for older adults to prioritize resistance exercise over aerobic exercise to maintain muscle mass and function.

Dr. Bikman concludes by emphasizing the societal benefits of maintaining muscle mass and combating anabolic resistance. Strong, healthy, and independent individuals contribute to stronger communities and reduced economic burdens. By adopting proper dietary and exercise habits, individuals can improve their muscle health, enhance their quality of life, and increase their longevity.

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01:08 - Defining Anabolic Resistance

02:15 - Impact of Aging on Muscle Protein Synthesis

03:15 - Role of Anabolic Stimuli in Muscle Growth

05:15 - Risks Associated with Loss of Muscle Mass

06:17 - Muscle's Role in Metabolic Health

07:19 - Muscle Mass and Longevity

10:24 - Age-Related Factors: Hormones and Physical Activity

11:10 - Biochemical Signaling and mTOR1 Pathway

13:28 - Controversy Around Rapamycin and Longevity

15:43 - Rapamycin's Impact on Muscle and Testosterone

17:42 - Nutrient Sensing and mTOR1 Activation

18:40 - Importance of Leucine in Protein Synthesis

19:54 - Hormonal Regulation of mTOR1

20:55 - Consequences of Anabolic Resistance

21:52 - Combating Anabolic Resistance: Dietary Strategies

24:05 - Importance of High-Quality Protein Sources

26:05 - Role of Resistance Exercise in Combating Anabolic Resistance

28:55 - Exercise Protocols for Older Adults

30:55 - Importance of Resistance Exercise Over Aerobic Exercise

32:55 - Conclusion and Societal Benefits of Muscle Health

References:

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Dr. Ben Bikman, professor of cell biology and metabolic scientist, delivers a lecture on the importance of fermentation and fermented foods from a metabolic perspective. He began by defining fermentation as the metabolic process where bacteria convert carbohydrates into organic molecules, emphasizing that bacteria primarily consume carbohydrates, not fats or proteins. Fermented foods such as dairy, vegetables, and beverages like kombucha and kefir are common examples. Fermentation not only changes the taste and texture of these foods but also has significant metabolic impacts.

A key benefit of consuming fermented foods is the reduction in glycemic load, which helps control blood sugar and insulin levels. Dr. Bikman highlightes studies showing that fermented milk improves glycemic control and lipid profiles in people with type 2 diabetes. He pointed out the importance of choosing genuinely fermented products, such as real sourdough bread, which lower postprandial glucose levels compared to conventional bread.

Dr. Bikman also discussed the production of short-chain fatty acids (SCFAs) during fermentation, such as acetate, propionate, and butyrate. These SCFAs have multiple health benefits, including improving gut health by maintaining gut barrier integrity, promoting an anti-inflammatory environment, and feeding gut cells. Additionally, SCFAs enhance metabolic functions, such as stimulating mitochondrial biogenesis and improving insulin sensitivity, which are crucial for overall metabolic health.

Fermented foods also provide probiotics when consumed raw and unpasteurized. These beneficial bacteria can help balance the gut microbiota, improve digestion, and support immune function. Dr. Bikman emphasizes the importance of incorporating raw, fermented foods into the diet to reap these probiotic benefits.

Lastly, Dr. Bikman introduced the concept of antinutrients, naturally occurring compounds in plant-based foods that can interfere with nutrient absorption. He explained that fermentation helps reduce the levels of antinutrients such as phytic acid, lectins, oxalates, and tannins, thereby enhancing the bioavailability of essential nutrients. He concludes by encouraging the incorporation of fermented foods into the diet as part of a strategy to control carbohydrate intake and improve metabolic health.

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01:00 – Overview of Fermentation

02:00 – Definition and Examples of Fermented Foods

04:00 – Benefits of Fermented Dairy: Kefir

06:00 – Fermented Foods and Glycemic Control

08:00 – Sourdough Bread vs. Conventional Bread

10:00 – Introduction to Short-Chain Fatty Acids (SCFAs)

12:00 – SCFAs and Gut Health

13:00 – SCFAs and Metabolic Benefits

15:00 – Probiotics in Fermented Foods

16:00 – Importance of Raw, Unpasteurized Fermented Foods

17:00 – Introduction to Antinutrients

18:00 – Examples of Antinutrients: Phytic Acid, Lectins, Oxalates, Tannins

20:00 – Fermentation's Role in Reducing Antinutrients

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References:

(Due to character length constraints, references are not posted here. For a complete list, please email: support@insuliniq.com with your request.)

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