Guanine nucleotide regulatory proteins in insulin's action and in diabetes

T h e detailed pathways which link occupancy of the insulin receptor with actions on target cells remain t o be defined. The insulin receptor expresses a tyrosyl kinase activity for which considerable evidence has accrued indicating that it plays a fundamental role in transducing at least certain o f insulin's actions. Nevertheless, the mechanism whcrcby tyrosyl phosphorylation o f proteins might lead to cellular responses is still as much of an enigma a s the physiological role o f the few substrates that have been identified 11.21. T h e functioning o f ii wide variety of cell surface receptors for hormones and neurotransmitters is transduced by their interaction with specific guanine nucleotide regulatory proteins (G-proteins) I3,4]. Not only that, but considerable evidence suggests that there is substantial 'cross-talk' bctwecn the machinery o f cellular signalling systems [ 51. This can lead to heterologous desensitization or t o supersensitization depending upon the signalling system and cell type. Here we discuss evidence which supports the contention we made earlier 16, 71, that insulin can interact with the G-protein system. This shows that ( i ) insulin, acting through its receptor can interact with both individual G-proteins and specific G-protein-controlled systems, ( i i ) that a specific G-protein may be involved in transducing certain of insulin's actions and ( i i i ) that in diabetes and in insulin-resistant states one sees the functional inactivation o f the inhibitory Gprotein G, in both liver 18.91 and white adipose tissue. MARY-ANNE McGREGOR. ELAINE KILGOUR.