Recombinant adiponectin does not lower plasma glucose in animal models of type 2 diabetes

• Published in: PloS one 2012-10, Vol.7 (10), p.e44270
• Main Authors: Tullin, Søren, Sams, Anette, Brandt, Jakob, Dahl, Kirsten, Gong, Wei, Jeppesen, Claus Bekker, Krogh, Thomas Nylandsted, Olsen, Grith Skytte, Liu, Yun, Pedersen, Anette Amstrup, Petersen, Jørn Meidahl, Rolin, Bidda, Wahlund, Per-Olof, Kalthoff, Christoph
• Format: Article
• Language: English
• Subjects: Adipocytes; Adiponectin; Adiponectin - genetics; Adiponectin - metabolism; Adiponectin - pharmacology; Animal models; Animals; Apolipoproteins; Atherosclerosis; Biological activity; Biology; Blood; Blood glucose; Blood Glucose - metabolism; Blood lipids; Body weight; Body Weight - drug effects; Cells (Biology); Chromatography, Gel; Cloning; Cloning, Molecular; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; DNA Primers - genetics; Electrophoresis, Polyacrylamide Gel; Gerbillinae; Glucose; Glycated Hemoglobin A - metabolism; Glycosylated hemoglobin; HEK293 Cells; Hemoglobin; Humans; Insulin; Kinases; Lipids; Lipids - blood; Low molecular weights; Mammalian cells; Medicine; Mice; Mice, Obese; Molecular weight; Mutagenesis, Site-Directed; Obesity; Oxidation; Phosphorylation; Proteins; Rats; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Rodents; Saccharomyces cerevisiae; Sand; Species Specificity; Type 2 diabetes; Weight control; Yeast; Yeasts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044270

Several studies have shown that adiponectin can lower blood glucose in diabetic mice. The aim of this study was to establish an effective adiponectin production process and to evaluate the anti-diabetic potential of the different adiponectin forms in diabetic mice and sand rats. Human high molecular weight, mouse low molecular weight and mouse plus human globular adiponectin forms were expressed and purified from mammalian cells or yeast. The purified protein was administered at 10-30 mg/kg i.p. b.i.d. to diabetic db/db mice for 2 weeks. Furthermore, high molecular weight human and globular mouse adiponectin batches were administered at 5-15 mg/kg i.p. b.i.d. to diabetic sand rats for 12 days. Surprisingly, none of our batches had any effect on blood glucose, HbA1c, plasma lipids or body weight in diabetic db/db mice or sand rats. In vitro biological, biochemical and biophysical data suggest that the protein was correctly folded and biologically active. Recombinant adiponectin is ineffective at lowering blood glucose in diabetic db/db mice or sand rats.