Fatty acids and insulin secretion

It has long been recognized that acute elevation of non-esterified fatty ac ids (NEFA) stimulates insulin secretion to a moderate extent both in vitro and in vivo. The effects of longer-term exposure to elevated fatty acids ha ve, however, been investigated only recently. Our own studies in the rat ha ve documented the time dependence of NEFA effects, with inhibition of gluco se-induced insulin secretion being apparent after 6-24 h in vivo exposure t o Intralipid or in vitro exposure to palmitate, oleate and octanoate. Evide nce indicates that the inhibitory effects are coupled to fatty acid oxidati on in B-cells, with ensuing reduction in glucose oxidation, in parallel wit h diminished activity of the pyruvate dehydrogenase enzyme. These findings were essentially confirmed in human pancreatic islets. In the db/db mouse, a model of type 2 diabetes with obesity, evidence was obtained for elevated NEFA playing a significant role in decreased glucose-induced insulin secre tion. Evidence also indicates that elevated NEFA inhibit insulin biosynthes is and increase the proinsulin : insulin ratio of secretion. Results on exp erimentally induced elevations of NEFA in non-diabetic and diabetic humans are thus far inconclusive. Further studies are needed to ascertain the impa ct of elevated NEFA on insulin secretion in clinical settings.