Enhanced metabolic cycling in subjects after colonic resection for ulcerative colitis.
Colonic resection leads to insulin resistance, but the mechanisms are unknown. We used an integrated approach to examine adipose tissue and skeletal muscle metabolism in patients lacking a colon. Ten healthy colectomized patients having undergone surgery for ulcerative colitis and 10 matched control subjects were studied with a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity, an arteriovenous sampling meal tolerance study to measure postprandial substrate flux across adipose tissue and skeletal muscle, and adipose tissue and skeletal muscle biopsies to quantify the expression of genes involved in glucose and lipid metabolism. Colectomized subjects exhibited lower insulin sensitivity (homeostatic model assessment model, 33% reduction, P = 0.03; minimal model, 29% reduction, P = 0.05), elevated aldosterone (9-fold, P = 0.003), leptin (2.2-fold, P = 0.03), and an increased rate of nonesterified fatty acid and glycerol release from adipose tissue (P = 0.02) especially in the late postprandial period. The uptake of fatty acids into muscle was also significantly increased (P = 0.007), as were muscle CD36 and LPL mRNA expression compared with controls. In adipose tissue, hormone-sensitive lipase mRNA expression was increased (P = 0.015), whereas peroxisome proliferator-activated receptor-gamma expression was decreased (P = 0.02), as was that of CD36 (P = 0.001). In this study, alterations in fatty acid metabolism after colonic resection altered may have contributed to the impairment of insulin sensitivity.
Robertson
M D
MD
Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, United Kingdom.
Bickerton
A S T
AS
Dennis
A L
AL
Vidal
H
H
Jewell
D P
DP
Frayn
K N
KN
D000328:Adult; D018955:CD36 Antigens / Q000235:genetics; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000601:surgery*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics; D002787:Sterol Esterase / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D005232:Fatty Acids, Volatile; D047495:PPAR gamma; D014280:Triglycerides; D002787:Sterol Esterase