Induction of a Glucose-Dependent Insulin Secretory Response by the Nonmetabolizable Amino Acid α-Aminoisobutyric Acid

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Abstract
The effects of the nonmetabolizable amino acid a-aminoisobutyric acid (AIB) on insulin release were evaluated using β cell-rich pancreatic 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 suppressed by clonidine or lowering of the temperature to 22°C. AIB effectively promoted the increase in sodium (total as well as ionized cytoplasmic) obtained with ouabain blockage of the Na/K pump. When added to a medium containing 11 mM glucose, AIB altered cytoplasmic Ca2+ in terms of both an initial transitory rise and transformation of existing oscillations into a sustained elevation. It is concluded that amino acids can stimulate insulin release from mature β cells by virtue of being cotransported with Na+.

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