Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys

• Published in: Diabetes (New York, N.Y.) Vol. 50; no. 5; pp. 1126 - 1133
• Main Authors: Hotta, Kikuko, Funahashi, Tohru, Bodkin, Noni L., Ortmeyer, Heidi K., Arita, Yukio, Hansen, Barbara C., Matsuzawa, Yuji
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.05.2001
• Subjects: Adipocytes; Adiponectin; Adipose Tissue - anatomy & histology; Amino Acid Sequence; Animals; Biological and medical sciences; Blood Glucose - metabolism; Body Weight; Cytochemistry; Development and progression; Diabetes Mellitus - blood; Diabetes Mellitus - physiopathology; Diabetes Mellitus - veterinary; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Diabetes Mellitus, Type 2 - veterinary; Diabetes. Impaired glucose tolerance; Disease Progression; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fat cells; Glucose Clamp Technique; Humans; Hyperinsulinism - blood; Insulin; Insulin - administration & dosage; Insulin - pharmacology; Intercellular Signaling Peptides and Proteins; Leptin - blood; Leptin - genetics; Macaca mulatta; Male; Medical sciences; Molecular Sequence Data; Obesity - blood; Obesity - physiopathology; Obesity - veterinary; Organ Size; Physiological aspects; Primate Diseases - blood; Primate Diseases - physiopathology; Proteins; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; Rhesus monkey; Sequence Alignment; Sequence Homology, Amino Acid; Type 2 diabetes; Japan; Endocrinopathy; Obesity; Pancreatic hormone; Adipose tissue; Pathophysiology; Monkey; Macaca mulatta; Gene expression; Non insulin dependent diabetes; Insulin; Protein; Blood plasma; Target tissue resistance; Metabolic disorder; Vertebrata; Mammalia; Primates; Simioidea
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.50.5.1126

Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys Kikuko Hotta 1 , Tohru Funahashi 1 , Noni L. Bodkin 2 , Heidi K. Ortmeyer 2 , Yukio Arita 1 , Barbara C. Hansen 2 and Yuji Matsuzawa 1 1 Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 2 Obesity and Diabetes Research Center, Department of Physiology, University of Maryland, Baltimore, Maryland Abstract Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients. This protein possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys ( Macaca mulatta ), which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and diabetic monkeys as in humans. Prospective longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes. Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake ( M rate). The plasma levels of adiponectin were significantly correlated to M rate ( r = 0.66, P < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the progression of insulin resistance. No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance. Footnotes Address correspondence and reprint requests to Kikuko Hotta, MD, Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan. E-mail: khotta{at}imed2.med.osaka-u.ac.jp . Received for publication 28 September 2000 and accepted in revised form 5 February 2001. AIR, acute insulin response; ELISA, enzyme-linked immunosorbent assay; FFM, fat-free mass; HSP83, heat shock protein 83; K G , glucose disappearance rate; M rate, insulin-stimulated glucose uptake rate; PAI-1, plasminogen activator inhibitor-1; PCR, polymerase chain reaction; RT, reverse transcriptase; TNF-α, tumor necrosis factor-α.