THE EFFECT OF THE GLUCAGON SUPPRESSORS PRAMLINTIDE AND EXENATIDE ON POSTPRANDIAL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The use of glucagon suppressors¿?? pramlintide and exenatide is well established in adult patients with T2DM, but there is a lack of information regarding an effective glucose lowering effect in pediatric T2DM. Previous studies from our laboratory showed that there is unabated early postprandial hyperglucagonemia in children with T2DM contributing to the marked postprandial hyperglycemia. There is insulin, amylin and GLP-1 deficiency in children with T2DM requiring insulin therapy. Both amylin and GLP-1 are potent endogenous glucagon suppressors. The glucose and glucagon lowering effect of the amylin analog pramlintide and the GLP-1 receptor agonist exenatide will be tested in insulin requiring children with T2DM. The lowest adult recommended doses would be used. With an increasing incidence of T2DM in the pediatric population, it is incumbent upon us to research new therapies in an effort to improve glycemic control and prevent the long-term micro and macrovascular complications associated with diabetes. We hypothesize that preprandial administration of a glucagon suppressor will decrease postprandial hyperglycemia and hyperglucagonemia in insulin treated children with T2DM. The objective is to determine the effect of the glucagon suppressors pramlintide and exenatide independently administered on: a) Glucose excursions b) Glucagon concentrations.