INDUCTION OF A GLUCOSE-DEPENDENT INSULIN SECRETORY RESPONSE BY THE NONMETABOLIZABLE AMINO-ACID ALPHA-AMINOISOBUTYRIC-ACID

The effects of the nonmetabolizable amino acid alpha-aminoisobutyric a cid (ALE) on insulin release were evaluated using beta cell-rich pancr eatic islets from ob/ob mice. Both AIB and L-alanine promptly induced transient insulin release during column perifusion of islet cells. The secretory response was dependent on an elevated level of glucose and effectively suppressed by removal of Na+. The insulin release elicited by AIB fulfilled the criteria of a physiological event in being suppr essed by clonidine or lowering of the temperature to 22 degrees C. AIB effectively promoted the increase in sodium (total as well as ionized cytoplasmic) obtained with ouabain blockage of the Na/K pump. When ad ded to a medium containing 11 mM glucose, AIB altered cytoplasmic Ca2 in terms of both an initial transitory rise and transformation of exi sting oscillations into a sustained elevation. It is concluded that am ino acids can stimu late insulin release from mature beta cells by vir tue of bring cotransported with Na+.