Metabolic effects of acute hyperketonaemia in man before and during an hyperinsulinaemic euglycaemic clamp.
1. The effects of acutely raising blood ketone body levels to those seen after 72 h of starvation were examined in 10 subjects after an overnight fast. Metabolic rate and respiratory exchange ratio were measured with indirect calorimetry before and during an insulin-glucose clamp. Arteriovenous differences were measured across forearm and subcutaneous abdominal adipose tissue. 2. In response to the clamp the respiratory exchange ratio rose from 0.82 to 0.83 during 3-hydroxybutyrate infusion and from 0.83 to 0.94 during control (saline) infusion (P < 0.001). 3. Forearm glucose uptake at the end of the clamp was 4.02 +/- 0.95 (3-hydroxybutyrate infusion) and 7.09 +/- 1.24 mmol min-1 100 ml-1 forearm (saline infusion). Whole body glucose uptake at the end of the clamp was 72.8 +/- 7.9 (3-hydroxybutyrate infusion) and 51.0 +/- 3.0 (saline infusion) mmol min-1 kg-1 body weight-1. 4. 3-Hydroxybutyrate infusion reduced the baseline abdominal venous-arterialized venous glycerol difference from 84 +/- 28 to 25 +/- 12 mmol/l and the non-esterified fatty acid difference from 0.60 +/- 0.17 to 0.02 +/- 0.09 mmol/l (P < 0.05 versus saline infusion). 5. Hyperketonaemia reduces adipose tissue lipolysis and decreases insulin-mediated forearm glucose uptake. Hyperketonaemia appears to prevent insulin-stimulated glucose oxidation, but does not reduce insulin-mediated glucose storage.
Webber
J
J
Department of Physiology and Pharmacology, Medical School, Nottingham, U.K.
Simpson
E
E
Parkin
H
H
Macdonald
I A
IA
D020155:3-Hydroxybutyric Acid; D000208:Acute Disease; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001481:Basal Metabolism / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood / Q000494:pharmacology; D007328:Insulin / Q000097:blood*; D007657:Ketone Bodies / Q000097:blood*; D008066:Lipolysis / Q000502:physiology; D008297:Male; D015657:Respiratory Transport / Q000502:physiology; D013217:Starvation / Q000378:metabolism*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007657:Ketone Bodies; D005990:Glycerol; D020155:3-Hydroxybutyric Acid