Do Diacylglycerides cause insulin Resistance in the liver or not?
At an earlier point in AMA #20 you talk about how Shulman did not see any reduction in liver glycogen synthesis in IR subjects due to the fact that the liver does not need Insulin to transport glucose into the liver, therefore the Diacylglycerides do not effect the glucose transport. In contrast to the muscle, which needs insulin to glucose to get in the cell and the Diacylglycerides cause a reduction of glycogen synthesis by impairing IRS1 which leads to the reduction in PI3K, and therefore the reduction in GLUT4 translocation, because the muscle cell needs insulin to triggers this process in order to allow glucose into the muscle cell.
Does Diacylglyceride effect liver glycogen synthesis?
Earlier in the AMA #20 Podcast you mention that Shulman saw no difference in the liver glycogen synthesis between insulin resistant patients and healthy patients. You explain the reason for this being that Diacylglyceride does not disrupt the glycogen synthesis in the liver due to the fact that the liver DOES NOT require insulin to transport glucose into the liver. The way in which Diacylglyceride generally disrupts glycogen synthesis (for example in the muscle) is through disrupting the process in which insulin drives glucose into the muscle, which DOES require insulin to drive glucose into the muscle cell. Therefore in the liver which does not need insulin to drive glucose into the cell Diacylglyceride would have no effect on liver glycogen synthesis. However, later in the podcast when explaining how insulin resistance manifests in the liver [1:09:15], you mention how the liver has something called insulin receptor substrate 2 and there is still a role of PI 3-kinase in the liver. You also mention diacylglycerides interfere with protein kinase Cs and that interferes with insulin signaling, and that’s what leads to this dysregulation and Dysregulation then leads to is an increase in de novo lipogenesis, an increase in the accumulation of intrahepatic fat. Additionally after that you mention "More insulin resistance in the liver, which would decrease hepatic glycogen storage because you don’t have any reason to be storing glucose at this point, you want to be kicking it out" So I am confused as to whether or not Diacylglyceride has an effect on liver glycogen synthesis or not. If it does as you seem to say later in the podcast, why did Shulman not see any difference in the liver glycogen synthesis between insulin resistant patients and healthy patients?