Regulation of somatostatin secretion in man: Study of the role of free fatty acids and ketone bodies

Abstract

We have investigated in normal subjects the possible role of plasma free fatty acids (FFA) and blood ketone bodies (KB) in the regulation of human somatostatin secretion. Heparin injected during the intravenous infusion of a fat emulsion raised FFA levels acutely from 0.4 ± 0.1 to near 3 mmol/L. Plasma somatostatin-like immunoreactivity (SLI) rose from a mean (±SEM) basal value of 9.2 ± 1.0 ng Eq S 14/L to 20.0 ± 6.0 ng Eq S 14/L ( P < 0.05). Plasma immunoreactive insulin (IRI) level was unchanged and glucagon (IRG) concentration decreased from 156 ± 20 to 107 ± 2 ng/L ( P < 0.05). During this test, there was a rise not only in FFA but also in plasma triglycerides (TG) and in blood glycerol and KB levels. The infusion of a fat emulsion alone increased triglyceride and glycerol levels to a similar extent but induced also a mild rise of FFA (0.37 ± 0.05 to 1.13 ± 0.5 mmol/L, P < 0.01), KB (78 ± 12 to 360 ± 45 μmol/L, P < 0.01), and SLI (14.8 ± 4.6 to 23.8 ± 7.1 ng Eq S 14/L, P < 0.05). The induction by dl-Na-3-hydroxybutyrate infusion of a rise of KB was associated with a decrease of FFA ( P < 0.05) and SLI ( P < 0.05) without modification of IRI or IRG levels. Phentolamine infusion did not modify the SLI or glucagon response to acute elevations of FFA, whereas propranolol suppressed the increase of SLI without preventing the concomitant decrease of IRG. These data suggest strongly that SLI secretion is stimulated in situations with high FFA levels in humans and that this effect is not mediated by the rise of KB. This increase of SLI seems to play no part in the concomitant decrease of IRG. The effect of propranolol suggests that the SLI response to metabolic stimuli could depend on the presence of basal β-adrenergic tone.