Thiazolidinediones enhance insulin-mediated suppression of fatty acid flux in type 2 diabetes mellitus.
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/m(2)) 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 (R(a)) 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 R(a) decreased progressively during each stage of hyperinsulinemia (P <.001). Suppression of palmitate R(a) by insulin was greater after than before troglitazone therapy (P <.001), whereas glycerol R(a) 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 R(a), possibly because of upregulation of lipoprotein lipase action on plasma triglycerides.
Racette
Susan B
SB
Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
Davis
Ajuah O
AO
McGill
Janet B
JB
Klein
Samuel
S
D000273:Adipose Tissue / Q000187:drug effects / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D002839:Chromans / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone