The Immediate Insulin-secretory Response of the Rat Pancreas to Glucose Compared with Tolbutamide and Other Secretagogues

Abstract

Insulin secretagogues induced characteristic secretory responses of the pancreas. While tolbutamide provoked an immediate insulin secretory response of the perfused rat pancreas, after a short delay insulin secretion appeared in response to glyceraldehyde, glucose, and mannose after different characteristic latent periods. Glucose and tolbutamide competed for insulin from the same rapidly available hormone pool during the immediate insulin-secretory response of the perfused pancreas. The mechanism of their secretory action differed. There was a latent period between arrival of glucose at the pancreatic β-cells and the insulin-secretory response when the perfu-sate was switched from a medium without glucose to a medium with 16.7 mM glucose. However, when the preperfusion medium contained a substimulatory glucose concentration, this latent period was diminished or nearly abolished. The increment in glucose concentration necessary for insulin release was reduced con-comitantly. The ability of glucose to sensitize pancreatic β-cells was concentration-dependent and time-dependent. Only mannose was able to substitute for glucose in its capacity to virtually abolish the latent period. Glyceraldehyde, dihydroxyacetone, and leucine only reduced the latent period. L-glucose, 3-O-methylglucose, fructose, and pyruvate were ineffective. Tolbutamide desensitized the β-cell to glucose stimulation and prolonged the latent period. It is proposed that both glucose and tolbutamide initiate insulin secretion by interaction with a common receptor site. They differ, however, in that glucose but not tolbutamide sensitizes pancreatic β-cells. Tolbutamide cannot fully replace glucose.