Taking Aim at Islet Hormones With GLP-1: Is Insulin or Glucagon the Better Target?

摘要

The last decade has seen a shift in the therapeutics of type 2 diabetes from insulin-centric to more multifarious approaches. Whereas previously drug treatment was based almost entirely on increasing insulin action-either by giving drugs to raise plasma insulin levels or to increase tissue responsiveness to insulin-it is now clear that addressing other processes controlling glucose metabolism is also fruitful. To wit, drugs that delay gastric emptying or carbohydrate digestion or promote renal glucose elimination have been shown to be effective for treating hyperglycemia. Compounds that affect hepatic glucose production directly or act through the central nervous system to lower blood glucose are in various phases of development. Moreover, glucagon, long known to contribute to abnormal glucose regulation in diabetes (1,2), is now amenable to therapeutic manipulation using drugs based on the naturally occurring hormones islet amyloid polypeptide (IAPP, also known as amylin) and glucagon-like peptide 1 (GLP-1).