Increase in diacylglycerol mass in isolated glomeruli by glucose from de novo synthesis of glycerolipids.
An increase in glucose concentration in the medium from 5 to 30 mM transiently enhanced diacylglycerol mass and activated protein kinase C in glomeruli isolated from nondiabetic rats as assessed by translocation of enzyme activity from the soluble to particulate fraction. Effects of glucose on both diacylglycerol mass and protein kinase C were evident at 5 and 15 min but waned by 30 min. An increase in glucose concentration in the medium also increased the incorporation of [14C]glucose into the glycerol backbone of diacylglycerol, triacylglycerol, and phospholipids. Several observations implied that [14C]glucose was being incorporated into diacylglycerol through the de novo pathway for glycerolipid synthesis rather than being derived from phospholipids. 1) [14C]glucose incorporation into all the lipids was suppressed by 2-deoxyglucose. 2) The incorporation of [14C]glucose into diacylglycerol and triacylglycerol was evident by 1 min and increased linearly for at least 30 min. In contrast, incorporation into phosphatidylcholine occurred with a lag of at least 5 min. 3) Although only 10% of the [14C]glucose incorporated into lipids was present in diacylglycerol versus greater than 50% in phospholipids, the specific activity of [14C]glucose in diacylglycerol was fivefold higher than that in phospholipid when expressed as a function of mass. 4) Glucose had no effect on labeled diacylglycerol or phosphatidic acid production in glomeruli that had been prelabeled with [3H]glycerol. Glucose-induced increases in diacylglycerol may contribute to the activation of glomerular protein kinase C observed in early diabetes.
Craven
P A
PA
Department of Medicine, University of Pittsburgh, Pennsylvania.
Davidson
C M
CM
DeRubertis
F R
FR
D000818:Animals; D003470:Culture Media; D003847:Deoxyglucose / Q000494:pharmacology; D004075:Diglycerides / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics / Q000494:pharmacology*; D005989:Glycerides / Q000378:metabolism*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D010743:Phospholipids / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D003470:Culture Media; D004075:Diglycerides; D005989:Glycerides; D008055:Lipids; D010743:Phospholipids; D003847:Deoxyglucose; D011493:Protein Kinase C; D005947:Glucose