Effects of metabolic inhibitors on the regulation of pancreatic glucagon release.

The effects of metabolic inhibition on the kinetics of glucagon release by pancreatic islets from normal guinea pigs have been studied in a perfusion system. All three metabolic inhibitors, malonate, iodoacetate and 2,4-dinitrophenol, induced a marked stimulation of glucagon secretion, each displaying its own characteristic pattern of response. This was accompanied by a rapid and marked decrease in the ATP concentration of the A2-cell as evidenced by measurements performed in A2-cell rich islets, isolated from guinea pigs treated with streptozotocin. The ATP levels were reduced by about 90% following iodoacetate and 2,4-dinitrophenol exposure and by about 60% after exposure to malonate. The data support the hypothesis that the inhibition of glucagon release from the A2-cell is regulated via an intracellular, energy-dependent mechanism.