Tissue and isoform-selective activation of protein kinase C in insulin-resistant obese Zucker rats - effects of feeding

• DOI: 10.1677/joe.0.1620207
• Publication Date: 2004-12-02T23:42:13Z
• Authors: X Qu; JP Seale; R Donnelly
• Keywords: Blood Glucose; Male; 0301 basic medicine; 2. Zero hunger; 0303 health sciences; Blotting, Western; Rats; Rats, Zucker; Diglycerides; Eating; 03 medical and health sciences; Animals; Insulin; Protein Kinase C

The mechanisms of insulin resistance in the obese Zucker rat have not been clearly established but increased diacylglycerol-protein kinase C (DAG-PKC) signalling has associated with decreased glucose utilisation states and non-insulin-dependent diabetes mellitus. purpose this study was to characterise tissue- isoform-selective differences DAG-PKC insulin-sensitive tissues from rats, assess effects feeding on pathways. Groups male (fa/fa, n=24) lean (fa/-, rats were studied after baseline measurements fasting serum glucose, triglycerides, oral tolerance tests. Liver, epididymal fat soleus muscle samples obtained fed overnight-fasted for DAG, PKC activity individual isoforms cytosol membrane fractions. Obese heavier (488+/-7 vs 315+/-9 g) hyperglycaemia (10.5+/-0.8 7.7+/-0.1 mM) hyperinsulinaemia (7167+/-363 251+/-62 pM) relative controls. In fasted fraction liver significantly higher group (174+/-16 108+/-12 pmol/min/mg protein, P<0.05) there no fat. state DAG levels threefold tissue expression major isoforms, PKC-theta PKC-epsilon: e.g. animals 283+/-42 (fed) 107+/-20 protein (fasting) compared 197+/-27 154+/-21 rats. conclusion, hepatic is under basal conditions feeding-induced activation occurs selectively (fa/fa) due DAG-mediated and/or synthesis PKC-epsilon. These changes are likely exacerbate hypertriglyceridaemia obesity-induced diabetes.