| First Author | Choudhary AK | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 10 | Pages | e78209 |
| PubMed ID | 24205160 | Mgi Jnum | J:209235 |
| Mgi Id | MGI:5566738 | Doi | 10.1371/journal.pone.0078209 |
| Citation | Choudhary AK, et al. (2013) Administration of heme arginate ameliorates murine type 2 diabetes independently of heme oxygenase activity. PLoS One 8(10):e78209 |
| abstractText | Amelioration of rodent type 2 diabetes by hemin has been linked to increased heme oxygenase (HO) activity, however alternative mechanisms have recently been proposed for its anti-diabetic effect. We sought to determine the anti-diabetic efficacy of heme arginate (HA), a clinically licensed preparation of heme, and whether its predominant mode of action is via increased HO activity. Intravenous administration of HA reduced hyperglycemia in diabetic (db/db) mice. Co-administration of the HO inhibitor stannous (IV) mesoporphyrin IX dichloride (SM) resulted unexpectedly in a further improvement in glycaemic control despite restoring HO activity to baseline levels. The anti-diabetic effects of HA+/-SM were associated with increased adiposity, increased serum adiponectin levels, reduced adipose tissue and islet inflammation and preservation of islet beta-cell function. HO activity independent effects of HA on adipogenesis and beta-cell inflammation were further confirmed in cell culture models using the 3T3-L1 pre-adipocyte and MIN6 beta-cell lines, respectively. In conclusion, our work demonstrates that the heme component of HA ameliorates experimental type 2 diabetes by promoting metabolically favourable adipogenesis and preserving islet beta-cell function, but this is not mediated via increased HO activity. |
