In this episode of The Metabolic Classroom Dr. Ben Bikman focused on the effects of alcohol on insulin resistance, emphasizing how ethanol, the main form of alcohol, influences the brain and metabolism. He highlighted that alcohol is primarily metabolized by the liver and can cause insulin resistance through both direct and indirect mechanisms. Dr. Bikman detailed the molecular pathways by which ethanol inhibits insulin signaling, notably by disrupting the insulin receptor substrate (IRS1) and increasing oxidative stress, which impairs insulin's ability to regulate glucose.

Ben provided evidence from studies demonstrating ethanol's impact on insulin resistance at the cellular and whole-body levels. Research showed that ethanol consumption leads to higher insulin responses during glucose tolerance tests, indicating a reduced sensitivity to insulin. This phenomenon was observed in healthy humans who experienced a significant increase in insulin levels after consuming alcohol, suggesting a profound metabolic shift due to ethanol's presence.

The lecture also covered indirect effects of alcohol on insulin resistance. Many alcoholic beverages contain high amounts of sugar, exacerbating insulin and glucose responses. Alcohol disrupts sleep quality, leading to poor metabolic outcomes and increased cortisol levels, which further contribute to insulin resistance. Additionally, ethanol competes with other metabolic substrates, leading to fat accumulation in the liver and elevated glucose and fat levels in the body.

Dr. Bikman concluded by discussing the inflammatory response triggered by alcohol, particularly through the concept of a "leaky gut," where ethanol causes gaps in intestinal cells, allowing harmful substances like lipopolysaccharides (LPS) to enter the bloodstream and induce inflammation. This inflammation promotes ceramide production, further contributing to insulin resistance. Overall, Dr. Bikman emphasized the significant role of alcohol in metabolic health issues and encouraged mindfulness regarding alcohol consumption to mitigate these risks.

01:10 - Alcohol and Metabolism

02:18 - Direct Effects of Ethanol

03:26 - Insulin Receptor Disruption

06:38 - Whole-Body Impact

08:37 - Ceramides and Insulin Resistance

11:34 - Indirect Effects: Sugar

13:31 - Indirect Effects: Sleep

18:37 - Indirect Effects: Substrate Competition

23:34 - Inflammation and Leaky Gut

Studies Referenced:

(see notes on YouTube video: https://youtu.be/1aMuPTre1IU )

https://www.insuliniq.com

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In this episode of The Metabolic Classroom, Dr. Bikman, a biomedical scientist and professor of cell biology, delves into the concept of energy toxicity.

He begins by explaining that energy toxicity attempts to explain why certain cells, particularly those capable of storing energy like muscle and liver cells, become insulin resistant. The primary idea is that when these cells accumulate excess energy, particularly in the form of triglycerides, they become resistant to further energy storage by becoming insulin resistant. He clarifies that this is closely related to lipotoxicity, where the stored fat itself, rather than glycogen, is seen as the main culprit for this condition.

Ben notes that while the notion of energy toxicity encompasses both glucose and fats, triglycerides, a type of fat stored in muscle and liver cells, play a significant role. However, studies, such as one on endurance athletes, have shown that muscle triglycerides alone do not cause insulin resistance, leading to the concept of the “athlete’s paradox.”

Dr. Bikman further explores the biochemical pathways involved in insulin resistance, emphasizing that specific lipid intermediates, particularly diacylglycerols (DAGs) and ceramides, are more relevant than triglycerides in causing insulin resistance. DAGs disrupt the insulin signaling pathway by activating protein kinase C, while ceramides inhibit insulin signaling and affect mitochondrial function, increasing reactive oxygen species and contributing to insulin resistance.

Ben challenges the notion of energy toxicity as a primary cause of insulin resistance, advocating instead for a focus on lipotoxicity and its mediators. He concludes that chronically elevated insulin levels, rather than the stored energy itself, are the main drivers of insulin resistance, suggesting that the term “insulin toxicity” might be more appropriate. This understanding is crucial for addressing what he identifies as the most common health issue worldwide—insulin resistance.

01:16: Defining Energy Toxicity

02:58: Lipotoxicity vs. Energy Toxicity

06:20: Ectopic Fat Storage

08:20: Triglycerides in Muscle Cells

13:57: The Athlete's Paradox

17:11: DAGs and Insulin Resistance

19:26: Ceramides and Mitochondrial Function

29:21: Insulin and Lipolysis

33:59: High Insulin and Insulin Resistance

Studies Referenced:

A phenomenon known as the “athlete’s paradox”:

https://academic.oup.com/jcem/article/86/12/5755/2849249

https://www.sciencedirect.com/science/article/abs/pii/S0165614717300962?via=ihub

https://www.sciencedirect.com/science/article/pii/S0021925820859080?via=ihub

https://www.jci.org/articles/view/43378

#MetabolicHealth #InsulinResistance #EnergyToxicity #Lipotoxicity #BenBikman #CellBiology #Triglycerides #DiabetesResearch #FatMetabolism #EctopicFat #KetogenicDiet #InsulinSensitivity #MitochondrialFunction #MetabolicClassroom #HealthScience #BiomedicalResearch #Endocrinology #Metabolism #HealthEducation #Type2Diabetes

https://www.insuliniq.com

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In this episode of The Metabolic Classroom, Dr. Bikman begins by emphasizing the critical role of insulin in regulating the body’s use of fuel, and influencing whether nutrients are stored or burned.

He highlights that food is a primary driver of insulin levels, but other factors like stress and sleep deprivation significantly impact insulin resistance.

Stress, often exacerbated by poor sleep hygiene, leads to elevated levels of cortisol and epinephrine, which in turn increase blood glucose levels. Ben explains that going to bed on a full stomach can worsen sleep quality, further contributing to insulin resistance.

Dr. Bikman discusses a study showing that restricting sleep to five hours per night for a week resulted in significant increases in cortisol and epinephrine, along with a notable decrease in insulin sensitivity. This chronic elevation of stress hormones due to poor sleep disrupts the natural circadian rhythm, causing a constant high level of cortisol, which not only hampers insulin function but also damages muscle, bone, and skin by promoting the breakdown of proteins for glucose production.

Dr. Bikman advises improving sleep hygiene, such as reducing evening snacking and dimming lights, rather than relying on stimulants like caffeine, which can exacerbate cortisol levels and insulin resistance.

00:57 - Impact of Stress on Insulin Resistance

01:59 - Effect of Evening Eating on Sleep Quality

02:59 - Study on Sleep Restriction and Insulin Sensitivity

04:10 - Stress Hormones and Sleep Deprivation

07:53 - Circadian Rhythm Disruption

08:54 - Cortisol’s Broader Effects

10:45 - Advice on Improving Sleep Hygiene

Studies referenced in this episode:

https://diabetesjournals.org/diabetes/article/59/9/2126/14525/Sleep-Restriction-for-1-Week-Reduces-Insulin

https://pubmed.ncbi.nlm.nih.gov/20371664/

#InsulinResistance #MetabolicHealth #DrBenBikman #Nutrition #Health #SleepDeprivation #StressManagement #Hormones #Cortisol #HealthyEating #SleepHygiene #InsulinSensitivity #Glucose #CircadianRhythm #KetogenicDiet #DiabetesPrevention #HealthTips #Wellness #Caffeine #HealthyLifestyle

https://www.insuliniq.com

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