The aim of this study is to evaluate the ability of a new drug, Exendin-4 (E4), to stimulate insulin release in volunteers with type 2 diabetes. Additionally, this drug may have insulin-like properties on its own, i.e., it may allow glucose to go into the cells of the body by its own action, as well as, by increasing insulin release. Insulin is known to allow glucose to enter cells of the body. Since E4 stimulates insulin, it is difficult to clearly estimate from the amount of glucose that goes into all cells of the body, how much is due to the increased insulin release, and how much to E4 per se. To answer this question, we will administer E4 to subjects with type 1 diabetes. Since in that condition (type 1) by definition, insulin release cannot be stimulated, any extra glucose that is taken up by the cells of the body must be due to direct effects of E4 per se. E4 is an agonist of a naturally occurring peptide released from the gut called GLP-1. The hyperglycemic clamp technique will be used to assess beta cell response to glucose before and after one month of subcutaneous administration of E4 in type 2 diabetes volunteers. After one hour of hyperglycemia, the plasma glucose will be allowed to return to basal levels for one hour. At this time (120 minutes after the start of the hyperglycemic clamp), a hyperinsulinemic-euglucemic clamp is quickly achieved and maintained for two hours in order to assess peripheral tissue sensitivity to insulin.
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