RESPONSIVENESS AND MEMORY OF THE PANCREATIC B-CELLS TO THE INSULIN SECRETAGOGUES D-GLUCOSE AND L-ARGININE IN PREDIABETIC AND DIABETIC RABBITS

Non-insulin-dependent diabetes was obtained in rabbits following pancreatic duct ligation. The insulin responses to D-glucose and to L-arginine were studied in the isolated perfused pancreas of control, prediabetic, and diabetic rabbits. In controls, D-glucose or L-arginine caused biphasic insulin release that was qualitatively and quantitatively altered in both prediabetic and diabetic animals. Most secretagogues influence the islet response to other secretagogues by modifying the B-cell memory. In perfused control pancreas, the priming effect of D-glucose resulted in a time-dependent potentiation (TDP) of insulin release during subsequent L-arginine stimulus, whereas L-arginine induced a time-dependent inhibition (TDI) of insulin release during subsequent D-glucose stimulus. As compared with the controls, the TDP effect obtained was emphasized in prediabetic and strongly diminished in diabetic animals. In some prediabetic and diabetic cases, the TDI remained unchanged compared with the controls, and in others it diminished in prediabetic and disappeared in diabetic animals where the effect became one of TDP. The effects of TDP and TDI seem to evolve independently of the modifications of the responsiveness to B-cell secretagogues.