Insulin increases distinct species of 1,2-diacylglycerol in isolated perfused rat heart.
Insulin and glucose increase the synthesis of 1,2-diacylglycerol (1,2-DAG), the physiological activator of protein kinase C (PKC) in a variety of tissues and cells. The effects of insulin and glucose on the abundance and fatty acid composition of 1,2-DAG were investigated in isolated perfused rat hearts with the use of capillary gas chromatography and 1,2-dipentadecanoin as an internal standard. A high concentration of insulin (25 mU/ mL) significantly increased cardiac contractility and reduced coronary flow. In addition, perfusion with 25 mU/mL insulin induced significant increases of 18.2% and 26.4% in 1,2-DAG mass after 5 and 30 minutes, respectively, in the presence of 8.6 mmol/L glucose, whereas there was no increase in 1,2-DAG with 2.5 mU/mL insulin. Analysis of the fatty acid composition of 1,2-DAG showed that only species containing specific fatty acids (16:0, 18:1, and 18:2) were increased in response to insulin. In contrast, an increase in glucose concentration in the perfusion medium from 3 to 17 mmol/L had no effect on the total mass or fatty acid composition of 1,2-DAG, cardiac contractility, or coronary flow. Addition of a high insulin concentration to the high-glucose medium increased the abundance of 1,2-DAG containing 16:0, 18:1, and 18:2 fatty acids, as well as cardiac contractility. It is concluded that the effect of insulin on cardiac contractility may be related to the associated increase in 1,2-DAG abundance.
Okumura
K
K
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Matsui
H
H
Murase
K
K
Shimauchi
A
A
Shimizu
K
K
Toki
Y
Y
Ito
T
T
Hayakawa
T
T
D000818:Animals; D004075:Diglycerides / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
C011439:1,2-diacylglycerol; D004075:Diglycerides; D005227:Fatty Acids; D007328:Insulin; D005947:Glucose