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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Recombinant adiponectin is ineffective at lowering blood glucose in diabetic db/db mice or sand rats.
Novo Nordisk A/S, Novo Nordisk Park, Måløv, Denmark. stu@novonordisk.com
Søren
S
Tullin
Anette
A
Sams
Jakob
J
Brandt
Kirsten
K
Dahl
Wei
W
Gong
Claus Bekker
CB
Jeppesen
Thomas Nylandsted
TN
Krogh
Grith Skytte
GS
Olsen
Yun
Y
Liu
Anette Amstrup
AA
Pedersen
Jørn Meidahl
JM
Petersen
Bidda
B
Rolin
Per-Olof
PO
Wahlund
Christoph
C
Kalthoff
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004591:Electrophoresis, Polyacrylamide Gel; D005849:Gerbillinae; D006442:Glycated Hemoglobin / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000097:blood; D051379:Mice; D008820:Mice, Obese; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae; D013045:Species Specificity
D052242:Adiponectin; D001786:Blood Glucose; D017931:DNA Primers; D006442:Glycated Hemoglobin; D008055:Lipids; D011994:Recombinant Proteins