Correction of abnormal small intestinal cytosolic protein kinase C activity in streptozotocin-induced diabetes by insulin therapy

• Published in: Biochemical journal 1990-12, Vol.272 (3), p.653-658
• Main Authors: WALI, R. K, DUDEJA, P. K, BOLT, M. J. G, SITRIN, M. D, BRASITUS, T. A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cytosol - enzymology; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - enzymology; Epithelium - drug effects; Epithelium - metabolism; Hormones. Endocrine system; Inositol Phosphates - metabolism; Insulin - therapeutic use; Intestine, Small - drug effects; Intestine, Small - metabolism; Kinetics; Male; Medical sciences; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Pharmacology. Drug treatments; Phosphatidylinositols - metabolism; Protein Kinase C - metabolism; Rats; Rats, Inbred Lew; Reference Values
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2720653

Diabetes was induced in rats by administration of a single intraperitoneal injection of streptozotocin (50 mg/kg body wt). After 7 days, one group of diabetic animals was treated with insulin for an additional 5 days. Control, diabetic and diabetic + insulin rats were then killed, their distal small intestines were removed and the epithelial cells were examined and compared with respect to polyphosphoinositide turnover, total protein kinase C activity and cellular distribution, and 1,2-diacylglycerol mass and production. The results of these experiments demonstrated that, compared with their control counterparts, the intestines from diabetic rats had a decreased turnover of polyphosphoinositides, but an increase in 1,2-diacylglycerol mass which was a result, at least in part, of an increase in the synthesis of this lipid de novo. Total protein kinase C activity was decreased in the diabetic rats due to a decrease in cytosolic activity, with no significant change in particulate activity. Moreover, insulin administration for 5 days to diabetic animals did not affect their lowered intestinal polyphosphoinositide turnover, but did further accentuate their increased 1,2-diacylglycerol mass and synthesis de novo; this treatment also corrected total protein kinase C activity by increasing the cytosolic activity of this enzyme. These results indicate that signalling mechanisms involving polyphosphoinositides, 1,2-diacylglycerol and protein kinase C are abnormal in the intestines of diabetic rats and that some of these biochemical parameters can be modulated by insulin administration in vivo.