This episode explores the complexities of insulin resistance, a prevalent metabolic condition underlying many chronic diseases. The conversation begins by establishing insulin resistance as a primary driver of type 2 diabetes, but also a significant contributor to cardiovascular disease, fatty liver disease, and various cancers. Against this backdrop, the guest details the use of NMR spectroscopy to measure glucose metabolism in vivo, revealing that in insulin-resistant individuals, glucose is not efficiently stored as glycogen in muscle, leading to its diversion to the liver and increased de novo lipogenesis. More significantly, the discussion delves into the molecular mechanisms of insulin resistance, pinpointing diacylglycerol (DAG) as a key bioactive lipid that disrupts insulin signaling pathways. For instance, the accumulation of DAG activates novel protein kinase C isoforms, inhibiting glucose uptake and promoting gluconeogenesis. The evolutionary basis of insulin resistance is also discussed, suggesting it serves a protective function during starvation by prioritizing glucose for the central nervous system. Ultimately, this detailed analysis highlights the importance of understanding insulin resistance for combating chronic diseases and suggests potential therapeutic avenues, such as targeting mitochondrial efficiency in the liver, to improve metabolic health.
