casein-kinase-ii and Hyperlipidemias

Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets.. Islets were cultured for 3 or 4 days at different glucose concentration with 0.5 mM palmitic acid (PA) or a 2:1 mixture of PA and oleic acid (OA) at 1% albumin (PA/BSA molar ratio 3.3). Afterwards, the response to glucose and acetylcholine were studied in perifusion experiments.. FA-induced impairment of insulin secretion and Ca. These results show that chronic FA treatment decreases acetylcholine potentiation of insulin secretion and that this effect is strictly glucose dependent and might involve CK2 phosphorylation of β-cell M3 muscarinic receptors.

Topics: Acetylcholine; Animals; Casein Kinase II; Cells, Cultured; Cholinergic Agents; Diabetes Mellitus, Type 2; Fatty Acids; Glucose; Humans; Hyperglycemia; Hyperlipidemias; Insulin; Insulin Secretion; Islets of Langerhans; Male; Mice; Receptors, Muscarinic; Signal Transduction