From glucose flux regulation to the control of atherosclerosis in type 2 diabetes mellitus.

Abstract

In healthy subjects, nutrients are rapidly absorbed after meals and, as soon as blood glucose concentrations start to rise, there is a rapid pulsatile insulin release. Portal insulin concentrations are increased and there is an immediate uptake of glucose by the liver while hepatic glucose output ceases, preventing excessive post-meal glycaemia. Subsequently, the glucose that passes through the liver raises blood glucose levels, and blood glucose is taken up by the muscle and adipose tissue in response to the raised insulin level. Therefore, glucose excursions are maintained within a narrow range due to the interaction between insulin and its target organs. Overnight blood glucose concentrations are also maintained within a narrow normal range since the rate of hepatic glucose output matches the rate of wholebody glucose utilisation, both rates being regulated by basal insulin secretion. In type 2 diabetes, glucose fluctuations are deranged due to impairment of the rapid pulsatile secretion of insulin in response to a rise in blood glucose, and a decline in the action of insulin on various insulin-sensitive tissues. In the early stages of diabetes even a small increase in insulin resistance, particularly in the liver, causes raised post-prandial blood glucose levels. The author has been investigating the factors promoting hepatic glucose uptake after mealintake, and seeking modalities to augment this process in order to facilitate strict glycemic regulation even after meal-intake. The ultimate goal of diabetes treatment is to prevent the progression of atherosclerotic changes. Furthermore, we have been investigating the molecular and cellular background of the natural history of type 2 diabetes mellitus. The author would like to express sincere gratitude to entire the staff of the Department.