人體內最主要的腸泌素 (incretin)— 昇糖素類似胜肽 (glucagon-like peptide 1， 簡稱
GLP-1)，是由遠端迴腸 (distal ileum) 及部分大腸 (colon) 所分泌的腸道荷爾蒙。食物會刺激GLP-1 由腸道分泌，進而根據血中葡萄糖濃度的上升程度，促進胰臟貝它細胞 (β cells) 之胰島素 (insulin) 分泌，抑制胰臟阿爾發細胞(α cells) 之昇糖素 (glucagon) 的分泌，以調節降低血中葡萄糖濃度。由於GLP-1 的作用依賴血中葡萄糖濃度而定，因此很少會引起低血糖的副作用。GLP-1 也會抑制屬於周邊器官組織之胃部的排空 (gastric emptying)，並且促使屬於中樞神經之下視丘產生飽足感 (satiety sensation)，造成抑制食慾及控制體重的效果。內生性的GLP-1 在人體會立刻被雙基胜肽酶-4 (dipeptidyl peptidase 4，簡稱DPP-4) 分解，轉變為不具生物學活性的代謝產物。利用腸泌素治療糖尿病，目前有兩種方式可以提升第二型糖尿病患者體內的腸泌素作用 (incretin action)：其一為施打不會被DPP-4 所分解的腸泌素類似物 (incretinmimetics)；其二為口服小分子的DPP-4 抑制劑 (DPP-4 inhibitor)。本文將探討腸泌素在第二型糖尿病治療的生物學背景以及其應用。

One of the major incretins in humans, glucagon-like peptide 1 (GLP-1), is a glucose-lowering, intestinalderived hormone secreted from distal ileum and part of the colon. Food intake stimulates GLP-1 secretion, which
in turn increases insulin secretion from pancreatic β cells, and suppresses glucagon secretion from pancreatic α cells. Because GLP-1 stimulates insulin secretion and inhibits glucagon secretion in a blood glucose-dependent manner, it rarely causes hypoglycemia. GLP-1 also increases central sensation of satiety and delays peripheral gastric emptying, thus has an anti-appetite and weight reduction effect. Once secreted, GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to form biologically inactive metabolites. Two strategies are applied to increase incretin action in type 2 diabetic patients, administration of injectable GLP-1 mimetics that are DPP-4 resistant and thus longer-acting, or of small molecule DPP-4 inhibitors to inhibit DPP-4 degradation of endogenous GLP-1 via oral route. In this review, incretin biology and the potential clinical use of incretin-based therapy in type 2 diabetes mellitus will be discussed.