Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man.
1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained. 2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h-1 kg-1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion. 3. On the Intralipid study day serum triacylglycerol (2.24 +/- 0.20 versus 0.67 +/- 0.10 mmol/l), plasma nonesterified fatty acid (395 +/- 13 versus 51 +/- 1 mumol/l), blood glycerol (152 +/- 2 versus 11 +/- 1 mumol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64-104) versus 4 (3-5) mumol/l] were all significantly higher (all P less than 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 +/- 0.07 versus 0.27 +/- 0.08 mg min-1 kg-1, P less than 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 +/- 0.77 to 6.17 +/- 0.71 mg min-1 kg-1, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
A B
AB
Department of Medicine, Royal Victoria Infirmary, Newcastle upon Tyne, U.K.
Argyraki
M
M
Thow
J C
JC
Cooper
B G
BG
Fulcher
G
G
Taylor
R
R
D020155:3-Hydroxybutyric Acid; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000201:enzymology*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D014280:Triglycerides; D006006:Glycogen Synthase; D005947:Glucose; D005990:Glycerol; D020155:3-Hydroxybutyric Acid