**6.1 IR in the liver**

A positive correlation has been demonstrated between fasting glucose and hepatic gluconeogenesis, such that as the latter descends, basal glycemia levels also descend. Therefore, the hepatic gluconeogenesis that produces glucose in an environment of elevated glycemia levels is abnormal and of very important in maintaining fasting hyperglycemia in DM2 patients. The mechanism through which hepatic glucose production increases would be an elevated supply of FFA from adipose tissue, which

through the metabolites of the Krebs cycle, serve as a substrate for gluconeogenesis. In the liver, at least two types of alterations have been found: the already mentioned increase in hepatic gluconeogenesis and an incapacity both of insulin and of glycemia to inhibit glucose production. In individuals with IR, the hepatic glucose cycle is increased due to a higher activity of glucose-6-phosphatase that dephosphorylates glucose-6-phosphate, which once dephosphorylated cannot be metabolized in the glycolysis such that glucose enters the circulation favoring hyperglycemia.
