%0 Journal Article
%T Administration of Heme Arginate Ameliorates Murine Type 2 Diabetes Independently of Heme Oxygenase Activity
%A Abhijeet K. Choudhary
%A Jillian Rennie
%A Carolynn Cairns
%A Gary Borthwick
%A Jeremy Hughes
%A Nicholas M. Morton
%A David Kluth
%A Bryan R. Conway
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0078209
%X 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¡ÀSM were associated with increased adiposity, increased serum adiponectin levels, reduced adipose tissue and islet inflammation and preservation of islet ¦Â-cell function. HO activity independent effects of HA on adipogenesis and ¦Â-cell inflammation were further confirmed in cell culture models using the 3T3-L1 pre-adipocyte and MIN6 ¦Â-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 ¦Â-cell function, but this is not mediated via increased HO activity.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078209