Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production.
To test the hypothesis that intrahepatic availability of fatty acid could modify the rate of suppression of endogenous glucose production (EGP), acipimox or placebo was administered before and during a test meal. We used a modified isotopic methodology to measure EGP in 11 healthy subjects, and (1)H magnetic resonance spectroscopic measurement of hepatic triglyceride stores was also undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal (0.05 +/- 0.01 mmol/l at -10 min, P = 0) and throughout the postprandial period (0.03 +/- 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly lower after the meal on acipimox days (8.9 +/- 0.4 vs. 10.1 +/- 0.5 mmol/l, P < 0.01), as was mean peak serum insulin (653.1 +/- 99.9 vs. 909 +/- 118 pmol/l, P < 0.01). Fasting EGP was similar (11.15 +/- 0.58 micromol.kg(-1).min(-1) placebo vs. 11.17 +/- 0.89 mg.kg(-1).min(-1) acipimox). The rate of suppression of EGP after the meal was almost identical on the 2 test days (4.36 +/- 1.52 vs. 3.69 +/- 1.21 micromol.kg(-1).min(-1) at 40 min). There was a significant negative correlation between the acipimox-induced decrease in peak plasma glucose and liver triglyceride content (r = -0.827, P = 0.002), suggesting that, when levels of liver fat were low, inhibition of lipolysis was able to affect glucose homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride stores improves postprandial glucose homeostasis without effect on the immediate postprandial suppression of EGP.
Dept. of Medicine, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Peter E
PE
Carey
Jean
J
Gerrard
Gary W
GW
Cline
Chiara
C
Dalla Man
Philip T
PT
English
Michael J
MJ
Firbank
Claudio
C
Cobelli
Roy
R
Taylor
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005502:Food; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000096:biosynthesis*; D005990:Glycerol / Q000097:blood; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010919:Placebos; D011719:Pyrazines / Q000494:pharmacology*; D014280:Triglycerides / Q000032:analysis / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D010919:Placebos; D011719:Pyrazines; D014280:Triglycerides; D005934:Glucagon; D005947:Glucose; C027696:acipimox; D005990:Glycerol