Abstract
Aims/HypothesisSeveral 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.MethodsHuman 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.ResultsSurprisingly, 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.Conclusions/InterpretationRecombinant adiponectin is ineffective at lowering blood glucose in diabetic db/db mice or sand rats.
Highlights
Adiponectin is a 30 kDa protein (244–247 amino acids, dependent on species) secreted exclusively by adipose tissue [1]
At least 3 different oligomeric adiponectin forms can be found in plasma: trimers, hexamers and high molecular weight (HMW) adiponectin [2,3,4]
The recombinant adiponectin batches generated for this study include the carboxy-terminal globular domain, low-molecular weight (LMW) as well as high molecular (HMW) forms
Summary
Adiponectin is a 30 kDa protein (244–247 amino acids, dependent on species) secreted exclusively by adipose tissue [1]. At least 3 different oligomeric adiponectin forms can be found in plasma: trimers, hexamers and high molecular weight (HMW) adiponectin [2,3,4]. The crystal structure of the trimeric globular form resembles the structure of TNFa [6] in spite of relatively low homology between the two proteins. The plasma concentration of adiponectin is usually in the range of 1–20 mg/l which is high for a hormone. The adiponectin plasma concentration correlates inversely with diabetes, obesity and cardiovascular disease (CVD) [7,8,9,10]. Adiponectin levels seem to be increased in chronic inflammatory conditions where the adipose tissue mass is not increased, e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and cystic fibrosis [11]
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