Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects.
Type 2 diabetic subjects failing glyburide therapy were randomized to receive additional therapy with either metformin (2,550 mg/day) or troglitazone (600 mg/day) for 3-4 months. Biopsies of subcutaneous abdominal adipose tissue were obtained before and after therapy. Glycemic control was similar with both treatments. Metformin treatment increased insulin-stimulated whole-body glucose disposal rates by 20% (P < 0.05); the response to troglitazone was greater (44% increase, P < 0.01 vs. baseline, P < 0.05 vs. metformin). Troglitazone-treated subjects displayed a tendency toward weight gain (5 +/- 2 kg, P < 0.05), increased adipocyte size, and increased serum leptin levels. Metformin-treated subjects were weight-stable, with unchanged leptin levels and reduced adipocyte size (to 84 +/- 4% of control, P < 0.005). Glucose transport in isolated adipocytes from metformin-treated subjects was unaltered from pretreatment. Glucose transport in both the absence (321 +/- 134% of pre-Rx, P < 0.05) and presence of insulin (418 +/- 161%, P < 0.05) was elevated after troglitazone treatment. Metformin treatment had no effect on adipocyte content of GLUT1 or GLUT4 proteins. After troglitazone treatment, GLUT4 protein expression was increased twofold (202 +/- 42%, P < 0.05). Insulin-stimulated serine phosphorylation of Akt was augmented after troglitazone (170 +/- 34% of pre-Rx response, P < 0.05) treatment and unchanged by metformin. We conclude that the ability of troglitazone to upregulate adipocyte glucose transport, GLUT4 expression, and insulin signaling can contribute to its greater effect on whole-body glucose disposal.
Ciaraldi
Theodore P
TP
VA San Diego Healthcare System and the Department of Medicine, University of California, San Diego, California 92161, USA.
Kong
Alice P S
AP
Chu
Neelima V
NV
Kim
Dennis D
DD
Baxi
Sunita
S
Loviscach
Mattias
M
Plodkowski
Ray
R
Reitz
Richard
R
Caulfield
Michael
M
Mudaliar
Sunder
S
Henry
Robert R
RR
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D001823:Body Composition; D002478:Cells, Cultured; D002839:Chromans / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000502:physiology*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology*; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D008687:Metformin; D000077288:Troglitazone