The effects of plasma lipid overload on pancreatic islet function and on mineral imbalance are issues under debate. However, the outcomes may be biased by the different metabolisms of different species. This prospective study evaluated whether a high fat diet intake changed the distribution of physiologically relevant elements within pancreatic endocrine and exocrine tissues of Sprague Dawley rats and New Zealand White rabbits. Nuclear microscopy techniques provided images of the specimen density and structure as well as the elemental distributions and quantification of P, S, Cl, K, Ca, Fe, and Zn using unstained cryosections of pancreas. Our results indicate that pancreatic islets in normal rats and rabbits had lower tissue density and higher Ca, Fe, and Zn content compared to exocrine tissue, and that rabbit islets exhibit the highest Zn content (3,300 μg/g in rabbits versus 510 μg/g in rats). Fat diet intake resulted in large deposits of fat in the pancreas, which modified the density contrast of tissues and also resulted in a twofold decrease of Ca and Zn concentrations in islets of both rats and rabbits. This result indicates that a fat diet leads to a reduction in essential trace element concentrations in pancreas, which in turn may hamper endocrine function.

It has long been recognized that acute elevation of non-esterified fatty acids (NEFA) stimulates insulin secretion to a moderate extent both in vitro and in vivo. The effects of longer-term exposure to elevated fatty acids have, however, been investigated only recently. Our own studies in the rat have documented the time dependence of NEFA effects, with inhibition of glucose-induced insulin secretion being apparent after 6–24 h in vivo exposure to Intralipid or in vitro exposure to palmitate, oleate and octanoate. Evidence indicates that the inhibitory effects are coupled to fatty acid oxidation in B-cells, with ensuing reduction in glucose oxidation, in parallel with 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 secretion. Evidence also indicates that elevated NEFA inhibit insulin biosynthesis and increase the proinsulin : insulin ratio of secretion. Results on experimentally induced elevations of NEFA in non-diabetic and diabetic humans are thus far inconclusive. Further studies are needed to ascertain the impact of elevated NEFA on insulin secretion in clinical settings.