Effects Of Glp-1 On Glucose Homeostasis

GLP-1是一种由肠道内分泌细胞产生的多肽，当非肠道给药时，可以使2型糖尿病患者的血糖正常化。其作用方式是通过一种特定的G蛋白偶联受体增加胰腺β细胞中的cAMP。在2002年之前，没有进行过慢性GLP-1输注的长期研究。在温哥华综合医院的Grady Meneilly博士和马萨诸塞州综合医院的Dariush Elahi博士的合作下，我们进行了一项为期3个月的研究，通过Mini Med泵持续皮下注射GLP-1。数据显示，该治疗没有快速反应，糖化血红蛋白维持在7%。这一数据证实了正在开发的治疗2型糖尿病的化合物是值得开发的，其作用机制是通过激活GLP-1受体 我们目前正在研究GLP-1的代谢作用，GLP-1是9-36酰胺片段。在体内，吃完后，碎片会在血浆中积累；因此，我们正在进行一项研究，以确定它本身是否具有生物学特性。我们已经发现，在胰岛素抵抗的受试者中，9-36酰胺会增加肝脏中的葡萄糖处置。我们目前正在研究 作用机制。

GLP-1, a peptide produced by the enteroendocrine cells of the gut, can normalize blood glucose in type 2 diabetes, when given parenterally. Its mode of action is by increasing cAMP in beta cells of the pancreas through a specific G-protein coupled receptor. Prior to 2002 no long-term studies with chronic GLP-1 infusions had been performed. In collaboration with Dr. Grady Meneilly, Vancouver General Hospital, and Dr. Dariush Elahi, Massachusetts General Hospital, we performed a 3-month study whereby we infused GLP-1 continuously subcutaneously via Mini Med pump. Data showed no tachyphylaxis to the treatment and it maintained a glycated hemoglobin of 7%. This data provides confirmation that compounds under development for type 2 diabetes, whose mechanism of action is via activation of the GLP-1 receptor, are worth developing We are now presently investigating the actions of a metabolic of GLP-1, the 9-36 amide fragment. In vivo, after eating, the fragment accumulates in the plasma; hence we are undertaking a study to ascertain if it per se has biological properties. We had found that 9-36 amide, in insulin-resistant subjects, increases glucose disposal in liver. We are currently working on the mechanism of action.