TY - JOUR
T1 - Thiazolidinediones enhance insulin-mediated suppression of fatty acid flux in type 2 diabetes mellitus
AU - Racette, Susan B.
AU - Davis, Ajuah O.
AU - McGill, Janet B.
AU - Klein, Samuel
N1 - Funding Information:
From the Departments of Internal Medicine and Pediatrics, Washington University School of Medicine, St Louis, MO. Submitted December 18, 2000; accepted August 7, 2001. Supported by a grant from Parke-Davis Pharmaceutical Research, Division of Warner-Lambert. Address reprint requests to Samuel Klein, MD, Washington University School of Medicine, 660 S Euclid Ave, Box 8031, St Louis, MO 63110-1093. Copyright © 2002 by W.B. Saunders Company 0026-0495/02/5102-0011$35.00/0 doi:10.1053/meta.2002.29981
PY - 2002
Y1 - 2002
N2 - Type 2 diabetes mellitus is characterized by insulin-resistant glucose and lipid metabolism. Thiazolidinediones (TZDs) enhance insulin-mediated glucose disposal, but their effects on lipid kinetics are unknown. We evaluated the effect of the TZD troglitazone on insulin-mediated suppression of fatty acid and glycerol kinetics. Eight obese men and women (body mass index [BMI], 34.1 ± 2.3 kg/m2) with insulin-requiring type 2 diabetes were studied before and after 12 weeks of troglitazone therapy (400 mg/d). Whole-body and abdominal fat masses were determined by dual-energy x-ray absorptiometry and magnetic resonance imaging, respectively. Palmitate and glycerol rates of appearance (Ra) into plasma were evaluated during a 3-stage hyperinsulinemic euglycemic clamp, which spanned the physiologic range of plasma insulin concentrations that regulate lipolysis. Troglitazone therapy did not alter body composition. Palmitate and glycerol Ra decreased progressively during each stage of hyperinsulinemia (P < .001). Suppression of palmitate Ra by insulin was greater after than before troglitazone therapy (P < .001), whereas glycerol Ra was unchanged. These results demonstrate that TZDs increase insulin-mediated suppression of fatty acid release into plasma in obese subjects with type 2 diabetes mellitus, which may contribute to their metabolic benefits. However, TZD therapy did not affect whole-body glycerol Ra, possibly because of upregulation of lipoprotein lipase action on plasma triglycerides.
AB - Type 2 diabetes mellitus is characterized by insulin-resistant glucose and lipid metabolism. Thiazolidinediones (TZDs) enhance insulin-mediated glucose disposal, but their effects on lipid kinetics are unknown. We evaluated the effect of the TZD troglitazone on insulin-mediated suppression of fatty acid and glycerol kinetics. Eight obese men and women (body mass index [BMI], 34.1 ± 2.3 kg/m2) with insulin-requiring type 2 diabetes were studied before and after 12 weeks of troglitazone therapy (400 mg/d). Whole-body and abdominal fat masses were determined by dual-energy x-ray absorptiometry and magnetic resonance imaging, respectively. Palmitate and glycerol rates of appearance (Ra) into plasma were evaluated during a 3-stage hyperinsulinemic euglycemic clamp, which spanned the physiologic range of plasma insulin concentrations that regulate lipolysis. Troglitazone therapy did not alter body composition. Palmitate and glycerol Ra decreased progressively during each stage of hyperinsulinemia (P < .001). Suppression of palmitate Ra by insulin was greater after than before troglitazone therapy (P < .001), whereas glycerol Ra was unchanged. These results demonstrate that TZDs increase insulin-mediated suppression of fatty acid release into plasma in obese subjects with type 2 diabetes mellitus, which may contribute to their metabolic benefits. However, TZD therapy did not affect whole-body glycerol Ra, possibly because of upregulation of lipoprotein lipase action on plasma triglycerides.
UR - https://www.scopus.com/pages/publications/0036179077
U2 - 10.1053/meta.2002.29981
DO - 10.1053/meta.2002.29981
M3 - Article
C2 - 11833043
AN - SCOPUS:0036179077
SN - 0026-0495
VL - 51
SP - 169
EP - 174
JO - Metabolism: clinical and experimental
JF - Metabolism: clinical and experimental
IS - 2
ER -