Effects Of Glp-1 On Glucose Homeostasis

GLP-1[7-36]酰胺是一种天然产生的促胰岛素多肽，在餐后状态下调节胰岛β细胞的胰岛素分泌。2型糖尿病患者需要药物剂量才能使血糖正常化。它是以30个氨基酸的形式产生的，但在几分钟内，N末端(HA)的前两个氨基酸被二肽基肽酶IV去除，使得剩余的GLP-1[9-36]酰胺失去了作为促胰岛素肽的活性。在餐后状态下，至少75%的GLP-1处于[9-36]形式。我们之前的研究人员发现，注射GLP-1[7-36]酰胺不仅增加了胰岛素的分泌，而且增加了肝脏中葡萄糖的处置，这与胰岛素无关。为了将GLP-1[7-36]酰胺从其代谢物[9-36]中分离出来，并与温哥华综合医院的Grady Meneilly医学博士和马萨诸塞州伍斯特大学的Dariush Elahi博士合作，我们一直在给瘦的和肥胖的受试者注射GLP-1[9-36]酰胺，以阐明它是否只有内在的代谢影响。我们发现，注射GLP-1[9-36]酰胺会增加肥胖受试者肝脏对葡萄糖的摄取，但不会增加瘦身受试者的肝脏葡萄糖摄取量。这反映了我们在GLP-1[7-36]酰胺输注中所发现的情况。葡萄糖摄取增加的作用机制仍未解决。

GLP-1 [7-36] amide is a naturally produced insulinotropic peptide which modulates insulin secretion from beta cells in the post-prandial state. Pharmacological doses are required to normalize blood glucose in type 2 diabetes. It is produced as a 30-amino acid peptide but within a few minutes the first two amino acids of the N-terminus (HA) are removed by a dipeptidyl peptidase IV, rendering the remaining GLP-1 [9-36] amide inactive as an insulinotropic peptide. In the post-prandial state, at least 75% of the GLP-1 is in the [9-36] form. Our previous investigators had found that GLP-1 [7-36] amide infusions not only increased insulin secretion but increased glucose disposal in liver, independent of insulin. In order to separate effects of GLP-1 [7-36] amide from its metabolite [9-36] and in conjunction with Grady Meneilly, M.D. (Vancouver General Hospital] and Dariush Elahi, Ph.D. (University of Worcester, MA) we have been infusing GLP-1 [9-36] amide to lean and obese subjects in order to elucidate if it had only intrinsic metabolic effects. We have found that GLP-1 [9-36] amide infusions result in increased glucose uptake by liver in obese, but not lean, subjects. This mirrors what we found with GLP-1 [7-36] amide infusion. The mechanism of action underlying the increased glucose uptake remains unresolved.