casein-kinase-ii and Hyperglycemia

Topics: Active Transport, Cell Nucleus; Animals; Casein Kinase II; Cell Nucleus; Hyperglycemia; Male; Myocytes, Cardiac; Rats; Rats, Wistar; Sarcoplasmic Reticulum

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

Changes in cellular free Zn

Topics: Animals; Blotting, Western; Casein Kinase II; Cation Transport Proteins; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Heart Ventricles; Hyperglycemia; Immunoprecipitation; Myocytes, Cardiac; Phosphorylation; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sarcoplasmic Reticulum; Zinc

We have used mRNA differential display to identify a novel high-glucose-regulated gene (HGRG-14) in human mesangial cells cultured for up to 21 days in 30 mM d-glucose. The mRNA of HGRG-14 seems to be regulated post-transcriptionally and encodes a small polypeptide of molecular mass 13 kDa. The native protein occurs as a dimer. The recombinant protein is a substrate for casein kinase II kinase. At high glucose concentrations, HGRG-14 protein levels decrease. This correlates with the appearance of a long form of HGRG-14 mRNA under high-glucose conditions. This form has a long 3' untranslated region containing several ATTTA RNA-destabilizing sequences and has a short half-life. A truncated, more stable mRNA that lacks the long 3' untranslated region is produced at 4 mM d-glucose. The switch from the truncated to the long-form transcript is detected within 2 h of exposure to 30 mM d-glucose, indicating that hyperglycaemic conditions have an acute effect on HGRG-14 mRNA processing.

Topics: 3' Untranslated Regions; Blotting, Northern; Blotting, Western; Carrier Proteins; Casein Kinase II; Cells, Cultured; Cloning, Molecular; Cross Reactions; Dactinomycin; Gene Expression Regulation; Glomerular Mesangium; Humans; Hyperglycemia; Phosphoproteins; Phosphorylation; Poly A; Protein Serine-Threonine Kinases; Recombinant Fusion Proteins; RNA, Messenger