Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy.
The relationship between insulin action and control of the adipocyte-derived factor adiponectin was studied in age- and weight-matched obese individuals with type 2 diabetes failing sulfonylurea therapy. After initial metabolic characterization, subjects were randomized to troglitazone or metformin treatment groups; all subjects received glyburide (10 mg BID) as well. Treatment was continued for 3 months. The extent of glycemic control after treatment was similar in both groups. However, the increase in maximal insulin-stimulated glucose disposal rate was greater following troglitazone therapy (+44%) compared with metformin treatment (+20%). Troglitazone treatment increased serum adiponectin levels nearly threefold. There was no change in serum adiponectin with metformin treatment. A positive correlation was found between increases in whole-body glucose disposal rates and serum adiponectin levels after troglitazone; no such relationship was seen with metformin. The adiponectin protein content of subcutaneous abdominal adipocytes was increased following troglitazone treatment and unchanged after metformin. Adiponectin release from adipocytes was also augmented with troglitazone treatment. Adiponectin was present in adipocytes and plasma in several multimeric forms; a trimer was the major form secreted from adipocytes. These results indicate that increases in adiponectin content and secretion are associated with improved insulin action but are not directly related to glycemic control. Modulation of adipocyte function, including upregulation of adiponectin synthesis and secretion, may be an important mechanism by which thiazolidinediones influence insulin action.
Phillips
Susan A
SA
VA San Diego HealthCare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Ciaraldi
Theodore P
TP
Kong
Alice P S
AP
Bandukwala
Rahil
R
Aroda
Vanita
V
Carter
Leslie
L
Baxi
Sunita
S
Mudaliar
Sunder R
SR
Henry
Robert R
RR
D017667:Adipocytes / Q000737:chemistry; D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001706:Biopsy; D002839:Chromans / Q000627:therapeutic use; D017077:Culture Media, Conditioned; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D008970:Molecular Weight; D009765:Obesity / Q000097:blood / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D013844:Thiazoles / Q000627:therapeutic use; D045162:Thiazolidinediones; D014018:Tissue Distribution; D000077288:Troglitazone
D052242:Adiponectin; D002839:Chromans; D017077:Culture Media, Conditioned; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D008687:Metformin; D000077288:Troglitazone; D005905:Glyburide