- 期刊
升糖素於糖尿病致病機轉角色探討回顧
Overview of the Role of Glucagon on the Pathogenesis of Diabetes
摘要
血糖控制對減緩糖尿病各種併發症扮演重要的角色。糖尿病的致病機轉相當複雜，目前已知胰島素分泌缺乏與胰島素阻抗為兩項主要的病生理缺陷。胰島素是調節身體血糖最重要的荷爾蒙，也是糖尿病患主要的治療方法之ㄧ。升糖素（glucagon）是另一種由胰臟α細胞分泌的荷爾蒙，其生理作用多與胰島素作用相反。研究顯示血中胰島素濃度乃調控α細胞分泌升糖素之重要因素。在低血糖時，血糖濃度下降而胰島素分泌也因而減少，此一變化會增加α細胞升糖素的分泌。相反地，進食之後血糖濃度上升與胰島素分泌增加，則會減少α細胞升糖素的分泌。在胰島素極度缺乏的第一型糖尿病或有胰島素分泌障礙的第二型糖尿病病人，β細胞功能衰退導致胰島素和升糖素之間喪失了互相調控功能，在低血糖時，因無正常狀態下胰島素分泌減少的情形，α細胞不會隨之增加升糖素的分泌，而減弱其應有使血糖提升之作用。相對的，在血糖濃度上升時，β細胞也無法製造足夠的胰島素來抑制α細胞之作用，使升糖素分泌持續增加與血糖更加上升。但如經由抑制升糖素的方法如給予體抑素（somatostatin）或腸泌素（incretins）等藥物，或利用升糖素受體剔除等技術，都可減緩因胰島素缺乏造成的高血糖與酮酸血症等代謝異常的發生。總而言之，在糖尿病的血糖控制與調控方面，除了考慮使用胰島素外，我們也應思考升糖素所扮演的角色，以助糖尿病血糖之控制。
並列摘要
Glycemic control plays an important role for prevention of vascular complications in diabetes. The pathogenetic mechanisms of diabetes are complex, and insulin deficiency and resistance are thought to be two main defects. It is well known that insulin is the most important hormone in the regulation of blood glucose and a main theraputic strategy of glycemic control in diabetes. Glucagon, another important islet hormone secreted by pancreatic cell, has an opposed physiological function to insulin. In experimental studies, insulin is shown to be involved in the regulation of α-cell glucagon secretion. A decrease in the plasma glucose concentration causes a decrease in β-cell insulin secretion that signals an increase in α-cell glucagon secretion during hypoglycemia. In contrast, an increase in the plasma glucose concentration, among other stimuli, causes an increase in β-cell insulin secretion that signals a decrease, or at least no change, in α-cell glucagon secretion after a meal. In type 1 diabetes and advanced type 2 diabetes, however, β-cell failure results in no decrease in β-cell insulin secretion and thus no increase in α-cell glucagon secretion during hypoglycemia and no increase in β-cell insulin secretion and thus an increase in α-cell glucagon secretion after a meal. In animal studies, suppression of glucagon function, such as by somatostatin, incretin-based therapy, or glucagon receptor-knockout technique, can alleviate hyperglycemia or ketoacidosis induced by insulin-deficiency, suggesting an important role of glucagon on diabetes. In summary, the coordinative roles between insulin and glucagon in the regulation of diabetic hyperglycemia should be rethought to achieve the maximal benefits to diabetes control.