Hormones of the VIP family are known to stimulate insulin secretion and to be implicated in glucose homeostasis. These hormones mediate their effect through activation of adenylyl cyclase (AC), and were recently shown to intervene in the maintenance of p-cells’ response to glucose in line with the “glucose competence concept.”’Glucagon and glucagon-like polypeptide (tGLP-1) are members of this family, for which the role in noninsulin-dependent diabetes (NIDDM) was lately highlighted. A mutation in the glucagon receptor was found to be highly associated with NIDDM, 2 while tGLP-1 has been proposed as a therapeutic agent in the treatment of NIDDM.) Nevertheless, the precise action of these two peptides on p-cells remains controversial. Studies have indicated a cross-reactivity between glucagon and tGLP-1 at the receptor level. 4 Thus one question that needs to be answered is whether j3-cells express specific receptors for glucagon and tGLP-I. Both glucagon and tGLP-1 receptors belong to the superfamily of the seven transmembrane spanning receptor^.^ This family of receptors are coupled to GTP binding proteins (G proteins) that regulate intracellular effectors, such as AC?’phospholipase C, 8 ionic channels;-l3 and others.’”’6 Several subfamilies of G proteins have also been identified. I7-l8 The presence of several G protein families has been demonstrated in different p-cell line^.'^^^^ However, the expression of these G proteins in the pancreatic p-cell still needs to be elucidated. In order to understand the precise regulatory role of glucagon and GLP-1 on insulin secretion, one must identify the presence of specific receptors as well as the G proteins mediating their action.