Copper (Cu) deficiency and arachidonic acid (AA) enhances insulin secretion in isolated pancreatic islets

Rats fed a Cu deficient diet have altered exocrine pancreatic function, however the effect of Cu deficiency on the endocrine pancreas is less well understood. Since Cu deficiency alters AA metabolism, and AA can modulate insulin secretion, we investigated the interaction of Cu deficiency and AA on glucose stimulated insulin secretion using isolated islets. Lean male (Fa/Fa) Zucker rats were fed either a Cu adequate (Cu+) or low Cu (Cu-) diet (8.7 vs 0.5 ug Cu/g diet) for 5 wk. Pancreatic islets were isolated and incubated in medium containing 3.3, 8.3. or 16.7 mM glucose with or without 100 uM AA. Insulin secretion was measured after either 5 (Phase I) or 45 (Phase II) min. In the absence of AA, islets from Cu- rats secreted more insulin during Phase I than those from Cu+ rats; there were no differences between the groups at Phase II. Endogenous AA treatment increased insulin secretion from islets during both phases of insulin secretion, regardless of dietary Cu treatment, at nearly all glucose levels. In the presence of AA. islets from Cu- rats secreted more insulin than from Cu+ rats at the 3.3 and 8.3 mM glucose levels, and at the 8.3 and 16.7 mM glucose levels during the 5 and 45 min incubations, respectively. Consistent with these findings, Cu- rats tended to have higher plasma insulin levels than Cu-)- rats (472.6 vs. 199.6 pM). In summary, Cu deficiency increases insulin release in isolated islets; this response is particularly pronounced when AA is present in the incubation medium.