METABOLISM OF ENDOGENOUS NUTRIENTS IN ISLETS OF GOTO-KAKIZAKI (GK) RATS

The metabolism of endogenous nutrients was examined in pancreatic isle ts of control and Goto-Kakizaki (GK) rats. At the ultrastructural leve l, no glycogen was found in the islet cells of GK rats, a situation si milar to that prevailing in normal islets. Likewise, by measuring the output Of L-lactate from islets first incubated at 16.7 MM D-glucose a nd then at 2.8 mM D-glucose, no evidence of glycogenolysis was found i n the islets of GK rats. The production of NH4+ and that of (CO2)-C-14 from islets prelabelled with either L-[U-C-14]glutamine or [U-C-14]pa lmitate were higher, however, in GK than in control rats. The changes in NH4+ and (CO2)-C-14 production evoked by D-glucose, by a non-metabo lized analogue of L-leucine (2-amino-bicyclo[2,2,1]heptane-2-carboxyli c acid; BCH) and by 3-phenylpyruvate were qualitatively comparable in control and GK rats. The secretory response to these three secretagogu es was severely decreased in the islets of GK rats. This coincided wit h an impaired enhancing action Of D-glucose on the conversion of [2-H- 3]glycerol into (HOH)-H-3. It is concluded that the catabolism of endo genous amino and fatty acids in islets is greater in GK than in contro l rats, especially at low D-glucose concentration. This may account, i n part at least, for the altered secretory response to BCH and 3-pheny lpyruvate. For glucose-induced insulin release, however, an impaired a cceleration of the glycerol phosphate shuttle apparently also particip ates in the secretory defect.