Effects of insulin on ketogenesis following fasting in lean and obese men.
The ketone bodies (KBs) D-3-hydroxybutyrate (D-3HB) and acetoacetate (AcAc) play a role in starvation and have been associated with insulin resistance. The dose-response relationship between insulin and KBs was demonstrated to be shifted to the right in type 2 diabetes patients. However, KB levels have also been reported to be decreased in obesity. We investigated the metabolic adaptation to fasting with respect to glucose and KB metabolism in lean and obese men without type 2 diabetes using stable glucose and D-3HB isotopes in a two-step pancreatic clamp after 38 h of fasting. We found that D-3HB fluxes in the basal state were higher in lean compared to obese men: 15.2 (10.7-27.1) vs. 7.0 (3.5-15.1) micromol/kg lean body mass (LBM) x min, respectively, P < 0.01. No differences were found in KB fluxes between lean and obese volunteers during the pancreatic clamp (step 1: 6.9 (1.8-12.0) vs. 7.4 (4.2-17.8) micromol/kg LBM x min, respectively; and step 2: 2.9 (0-7.2) vs. 3.4 (0.85-18.7) micromol/kg LBM x min, respectively), despite similar plasma insulin levels. Meanwhile, peripheral glucose uptake was higher in lean compared to obese men (step 1: 15.2 (12.3-25.6) vs. 14.7 (11.9-22.7) micromol/kg LBM x min, respectively, P < or = 0.05; and step 2: 12.5 (7.0-17.3) vs. 10.8 (5.2-15.0) micromol/kg LBM x min, respectively, P < or = 0.01). These data show that obese subjects who display insulin resistance on insulin-mediated peripheral glucose uptake have the same sensitivity for the insulin-mediated suppression of ketogenesis. This implies differential insulin sensitivity of intermediary metabolism in obesity.
Soeters
Maarten R
MR
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.r.soeters@amc.uva.nl
Sauerwein
Hans P
HP
Faas
Linda
L
Smeenge
Martijn
M
Duran
Marinus
M
Wanders
Ronald J
RJ
Ruiter
An F
AF
Ackermans
Mariëtte T
MT
Fliers
Eric
E
Houten
Sander M
SM
Serlie
Mireille J
MJ
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D004734:Energy Metabolism / Q000502:physiology; D004837:Epinephrine / Q000097:blood; D005215:Fasting / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D007657:Ketone Bodies / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D013851:Thinness / Q000378:metabolism*; D055815:Young Adult
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine