As a crossroad between carbohydrate and lipid metabolism, pyruvate carboxylase expression in gluconeogenic tissues, adipose tissues and pancreatic islets must be coordinated. In conditions of over nutrition, PC levels are increased in pancreatic β-cells to increase pyruvate cycling in response to chronically elevated levels of glucose. In contrast, PC enzyme levels in the liver are decreased by insulin; during periods of overnutrition adipocyte tissue is expanded with extreme expression of PC and other lipogenic enzymes. Hepatic control of glucose levels is still regulated in an over nutrition situation, but in obesity induced type 2 diabetes the regulation of peripheral glucose levels is no longer under regulation of insulin.