The effect of diabetes on phosphatidylinositol turnover and calcium influx in myocardium.
Diabetes was induced in rats by administration of streptozotocin. Diabetes occurred within 24 h after treatment. Two forms of diabetes were studied, an acute form (4 days) and a chronic form (2 months). In a separate experiment the effect of insulin and an aldose reductase inhibitor on acute diabetes was studied. Phosphoinositide labelling was done in biopsies of heart with [3H] myo-inositol. It was shown that the incorporation of myo-inositol amounted to about 65% in acute diabetes and 80% in chronic diabetes compared to age-matched controls. The incorporation both in atria and ventricles was affected in a similar way. Muscarinic receptor-mediated phosphatidylinositol breakdown and release of myo-Ins-1 P (myo-inositol 1-phosphate) was unaffected in diabetic hearts in the chronic model. In hearts of diabetic ketotic animals uncoupling of the muscarinic receptor from the phosphoinositide metabolism was apparent. Calcium net influx was significantly reduced in both acute and chronic diabetes compared to age-matched controls. Insulin supplementation to acute diabetic animals significantly improved phosphoinositide labelling with [3H] myo-inositol. No improvement was seen in calcium transport. An aldose reductase inhibitor also facilitated phosphoinositide labelling without improving calcium transport. It is suggested that phosphoinositide metabolism and calcium entry through the slow inward current are independent of one another and the former is sensitive to insulin. It is suggested that insulin by regulating the pool of phosphoinositides and release of endogenous calcium may modulate cardiac function.
Bergh
C H
CH
Wallenberg Laboratory, University of Göteborg, Sahlgren's Hospital, Sweden.
Hjalmarson
A
A
Sjögren
K G
KG
Jacobsson
B
B
D000818:Animals; D001706:Biopsy; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; C002647:inositol 1-phosphate; D002118:Calcium