Abstract
Blood glucose levels are tightly controlled in normal subjects: 70-110 mg/dl in the fasting state and below 140 mg/dl two hours after 75 g oral glucose challenge. Brain uses glucose at very high rate, 5 g/hr. Suppose the circulating blood volume being 5 l, the subject with 100 mg/dl glucose level has 5 g glucose in the blood. Therefore, glucose levels would decrease to zero in one hour if there were no supply of glucose to the circulation. 75 g oral glucose challenge would give rise to 1500 mg/dl blood glucose. However, these things never happen. I will focus on three issues in my talk. 1) Glucose transport requires conformational change of membrane protein termed glucose transporter and C-terminal deletion locks glucose transporter into an inward-facing form without transport activity. Similar mutations reportedly caused human disease. For insulin stimulation of glucose transport, insulin receptor, IRS, PI3 kinase, Akt and glucose transporter GLUT4 are sequentially stimulated. 2) Tight control also depends on glucose-regulated insulin secretion. A key molecule for recognition of blood glucose levels is glucokinase in beta cells and mutations of this gene cause diabetes. Clinical characteristics of these patients we found are consistent with the role of glucokinase in insulin secretion. 3) To understand the disease such as diabetes, not only a role of a specific molecule in cells but also cross-talk between cell and cell, tissue and tissue, and overall whole body metabolism are of much interest. I will discuss brain sensing and regulation of peripheral metabolism through autonomic nervous system. [Jpn J Physiol 55 Suppl:S4 (2005)]
