The invention herein provides a mode of treating metabolic syndrome, which includes Type 2 diabetes mellitus and insulin resistance in human and other subjects by identifying and administering an insulin sensitizing compound which modulates GRK2 function in the insulin signaling pathway. The invention also provides polynucleotides, polypeptides, vectors, cells, tissues and organisms useful in the identification and treatment of metabolic syndrome. A number of desirable insulin sensitizing aspects are achieved by various embodiments of the present invention.