Correction of abnormal small intestinal cytosolic protein kinase C activity in streptozotocin-induced diabetes by insulin therapy.
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.
Wali
R K
RK
Department of Medicine, Pritzker School of Medicine of the University, Chicago, IL 60637.
Dudeja
P K
PK
Bolt
M J
MJ
Sitrin
M D
MD
Brasitus
T A
TA
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values
D007295:Inositol Phosphates; D007328:Insulin; D010716:Phosphatidylinositols; D011493:Protein Kinase C