Effect of short-chain fatty acids on the secretory response of the ovine exocrine pancreas.

The secretory response of the exocrine pancreas to short-chain fatty acids has been studied in anesthetized sheep and in isolated lobules. Butyrate, propionate, and acetate stimulated pancreatic juice flow and protein and amylase output in the anesthetized sheep. The secretory response to butyrate was significantly greater than that of propionate or acetate. Rapid intravenous injection of butyrate (625 mumol/kg) caused a 13-fold rise in the juice flow, 26-fold in protein output, and 37-fold in amylase output above the basal levels within 5 min and declined to basal levels over a period of 30 min. Responses to butyrate (625 mumol/kg) were comparable with those obtained with 2 U/kg pancreozymin (Boots). Detectable responses were obtained with 15 mu/kg butyrate, 125 mumol/kg propionate, and 312.5 mumol/kg acetate. The secretory response to butyrate (625 mumol/kg) was not affected by pretreatment with atropine and hexamethonium. In the isolated lobule preparation, amylase release increased in response to butyrate in a concentration-dependent manner, reaching a maximal level at 1 mM and declining at 100 mM. It is concluded that short-chain fatty acids act directly on pancreatic acinar cells to stimulate secretion. The physiological implications of these findings are considered.