The Regulation of Adenylate Cyclase Activity in Murine Models of Type II Diabetes Mellitus

It is now well-established that many hormones regulate the metabolism of target cells by binding to receptors which can interact with specific members of a family of guanine nucleotide-binding regulatory proteins (G-proteins) which can in turn control the activity of various intracellular effector enzymes and ion channels. One such effector enzyme is adenylate cyclase which is controlled by stimulatory (Gs) and inhibitory (Gi) proteins. Both of these proteins are heterotrimers consisting of alpha-, beta- and gamma-subunits, with the alpha-subunits conferring the abilities to interact with particular receptors and effectors. There are at least three members of the Gialpha-subunit family of proteins, termed Gialpha-1, Gialpha-2 and Gialpha-3. The functional significance of this multiplicity is unknown although it has been suggested that Gialpha-2 may be responsible for mediating the inhibition of adenylate cyclase activity in certain systems and that each of these proteins can regulate K+ channel opening