AJP - Endocrinology and Metabolism, Vol 267, Issue 2 E234-E241, Copyright © 1994 by American Physiological Society
Chemical specificity of short-chain fatty acids in stimulating insulin and glucagon secretion in sheep
H. Mineo, Y. Hashizume, Y. Hanaki, K. Murata, H. Maeda, T. Onaga, S. Kato and N. Yanaihara
Department of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.
The chemical specificity and structural requirements of short-chain fatty
acids (SCFAs) in stimulating pancreatic endocrine responses was
investigated in conscious sheep. Normal SCFAs with one to eight carbons
were injected intravenously at seven doses of 39-2,500 mumol/kg body wt.
The isomers or derivatives of SCFAs were administered at 625 mumol/kg body
wt. Analysis of dose-response curves showed that n-butyric acid (4 carbons
in the molecule) was most effective for both insulin and glucagon secretion
among the normal SCFAs tested. In addition, one carboxylic group was
absolutely required, since hormone secretion was significantly reduced or
abolished with compounds in which the carboxylic element was replaced by
other groups and with dicarboxylic acids. The form of the hydrocarbon chain
(branched, cyclic, or benzoic ring) also affected hormone secretory
activity. Most of the compounds that replaced hydrogen in the hydrocarbon
chain by other groups at various positions reduced or abolished the hormone
secretory effect obtained by n-butyric acid. In conclusion, a
monocarboxylic acid with several numbers of hydrocarbons was required for
insulin or glucagon secretion. These results suggest that the pancreatic
endocrine system can recognize the chemical structure of SCFAs in detail
and induce hormone secretion in sheep.
