title: Anti-CD44 antibody treatment lowers hyperglycemia and improves insulin resistance, adipose inflammation, and hepatic steatosis in diet-induced obese mice.
abstract: Type 2 diabetes (T2D) is a metabolic disease affecting >370 million people worldwide. It is characterized by obesity-induced insulin resistance, and growing evidence has indicated that this causative link between obesity and insulin resistance is associated with visceral adipose tissue inflammation. However, using anti-inflammatory drugs to treat insulin resistance and T2D is not a common practice. We recently applied a bioinformatics methodology to open public data and found that CD44 plays a critical role in the development of adipose tissue inflammation and insulin resistance. In this report, we examined the role of CD44 in T2D by administering daily injections of anti-CD44 monoclonal antibody (mAb) in a high-fat-diet mouse model. Four weeks of therapy with CD44 mAb suppressed visceral adipose tissue inflammation compared with controls and reduced fasting blood glucose levels, weight gain, liver steatosis, and insulin resistance to levels comparable to or better than therapy with the drugs metformin and pioglitazone. These findings suggest that CD44 mAb may be useful as a prototype drug for therapy of T2D by breaking the links between obesity and insulin resistance.
authors.affiliation: Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA Lucile Packard Children's Hospital, Palo Alto, CA kkodama@stanford.edu abutte@stanford.edu.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kodama
authors.affiliation: Division of Biomedical Research Center, Biomedical Laboratory, Kitasato Institute Hospital, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Toda
authors.affiliation: Department of Diagnostic Pathology, Kitasato Institute Hospital, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Shojiroh
authors.initials: S
authors.lastname: Morinaga
authors.affiliation: Diabetes Center, Kitasato Institute Hospital, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Systems Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA Lucile Packard Children's Hospital, Palo Alto, CA kkodama@stanford.edu abutte@stanford.edu.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000188:drug therapy* / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors