Influence of Plasma Free Fatty Acids on Pancreatic Polypeptide Secretion in Man*

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Abstract
We have examined the influence of changes in the concentration of plasma free fatty acids (FFA) on human pancreatic polypeptide (hPP) secretion in normal subjects. During iv infusion of a lipid emulsion plus heparin, mean (± SE) plasma hPP declined progressively from a fasting value of 65 ± 10 to a nadir of 25 ± 7 pg/ml (P < 0.001), while circulating FFA rose from 674 ± 47 to a peak of 5756 ± 650 /eq/liter. When lipid was given without heparin, the mean hP concentration also decreased from 49 ± 6 to 26 ± 4 pg/ml (P < 0.001; maximal FFA level, 3845 ± 348 /neq/liter). Similarly, the injection of heparin was followed by a reduction of circulating hPP, from 67 ± 10 to 29 ± 9 pg/ml (P < 0.0001), and a simultaneous elevation of plasma FFA (peak, 1145 ± 225 jueq/liter). To evaluate the effect of high plasma FFA levels on the hPP response to food intake, aprotein-rich meal was given during the infusion of either lipid plus heparin or normal saline. Lipid administration depressed basal hPP levels and markedly inhibited the hPP riseinduced by the meal (peaks, 162 ± 36 us. 267 ± 58 pg/ml in the saline experiment; P < 0.05). On the other hand, iv nicotinic acid was followed by a decrease of plasma FFA with only a modest and delayed rise of circulating hPP, seemingly unrelated to the drop in FFA. These results demonstrate that experimental maneuvers which provoke intense elevationsof plasma FFA induce a clear depression of circulating hPP levels and reduce markedly theresponse of this hormone to feeding in normal subjects. In contrast, it does not seem likely that a fall in the concentration of these substrates in blood is able to stimulate hPP release.