Effects of Iodoacetate, Mannoheptulose and 3-O-Methyl Glucose on the Secretory Function and Metabolism of Isolated Pancreatic Islets

The ability of iodoacetate, mannoheptulose, and 3-O-methyl glucose to alter islet cell metabolism and glucose-stimulated insulin secretion was examined. A method for the sequential analysis of the releasing and fuel function of glucose in isolated islets was applied. Insulin release was measured by radioimmunoassay and the metabolism of glucose by determining the rate of tritiated water production from [5-3H]glucose and lactate accumulation. It was found that iodoacetate, in the range of 0.2-1.0 mM, inhibited the metabolism of glucose linearly while release was not blocked until metabolism was reduced by 30-40%. The KI for both processes, release and metabolism, was the same. Pyruvate did not protect against or reverse the effects of iodoacetate. Mannoheptulose inhibited both release and metabolism half-maximally at about 5 mM when 27.5 mM glucose was used as the stimulatory agent. A mannoheptulose-resistant component of glucose metabolism, amounting to 30% of the maximal rate was observed. 3-O-Methyl glucose had no effect on insulin release but reduced glucose utilization and lactate production from low glucose. The results are discussed in light of the two prevailing hypotheses explaining glucose induced insulin release, i.e., the receptor and the metabolism hypotheses.