Prompt Cast
Understanding Insulin Resistance Mechanisms and Implications
TLDR Raising fatty acids through a triglyceride and heparin infusion can cause insulin resistance, leading to various chronic diseases. Insulin resistance progresses from muscle to liver in humans, unlike in rodents, and can be improved with exercise.
Timestamped Summary
00:00
The episode is a masterclass on insulin resistance, covering its mechanisms, clinical implications, and the role of diet, exercise, and pharmacologic agents.
07:06
Insulin resistance is a key factor leading to type two diabetes and various other chronic diseases, including atherosclerosis, hyperlipidemia, fatty liver disease, and cancer.
14:15
A method using C13 NMR can track the metabolization of labeled glucose within cells, providing insights into intracellular pathways and flux without ionizing radiation.
21:46
Insulin resistance in muscle is linked to fatty liver and liver insulin resistance, potentially leading to type 2 diabetes.
29:15
Insulin resistance in muscle is linked to fat inside the muscle cell, which is the best predictor for insulin resistance and block in glucose transport.
36:36
Raising fatty acids through a triglyceride and heparin infusion causes insulin resistance by interfering with insulin activation of transport in muscle cells.
44:16
Excess fatty acids entering muscle cells can lead to insulin resistance by causing an accumulation of diacylglycerol, which interferes with insulin signaling pathways.
51:58
Insulin resistant individuals show increased de novo lipogenesis and impaired hepatic glucose sensitivity, leading to elevated triglycerides and reduced HDL levels, setting them up for metabolic associated fatty liver disease and potential future liver complications.
59:31
Young, lean, healthy individuals with insulin resistance due to parental diabetes show improved muscle glucose uptake and insulin sensitivity with exercise, potentially reducing the risk of fatty liver and metabolic complications.
01:06:59
Insulin resistance in humans progresses from muscle to liver, unlike in rodents, where liver insulin resistance precedes muscle insulin resistance.
01:14:32
Insulin resistance may exist as a protective mechanism during starvation to promote glucose circulation for the CNS, allowing species to survive in times of limited food availability.
01:22:15
Insulin regulates glucose homeostasis through modulation of gluconeogenesis, primarily by affecting peripheral lipolysis to control fatty acid delivery to the liver and acetyl-CoA content.
01:29:50
Insulin resistance in the fat cell leads to increased lipolysis and contributes to fasting hyperglycemia in poorly controlled type 2 diabetes.
01:37:21
Visceral fat is a strong predictor of insulin resistance and contributes to the accumulation of fat in the liver, which plays a significant role in driving metabolic diseases like diabetes.
01:44:32
GLP1 agonists lead to weight loss and reversal of fatty liver through reduced appetite and central mechanisms.
01:51:42
Liver-specific uncoupling can potentially melt away fat within the liver without toxicity, increasing the therapeutic window for treating important metabolic diseases.
01:58:53
Metformin at clinically relevant doses inhibits gluconeogenesis from glycerol and lactate, but not from other substrates, potentially explaining the lack of hypoglycemia in patients treated with metformin.
Categories:
Health & Fitness
