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Mesenchymal stem cell therapy to promote peripheral tissue insulin sensitivity in the high‐fat fed, myocardial infarcted mouse
Author(s) -
Hughey Curtis,
Ma Lianli,
James Freyja D,
Bracy Deanna P,
Wasserman David H,
Rottman Jeffrey N,
Shearer Jane
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1010.17
Subject(s) - medicine , endocrinology , insulin resistance , adipose tissue , insulin , mesenchymal stem cell , myocardial infarction , peripheral , glucose uptake , transplantation , glucose clamp technique , insulin sensitivity , pathology
OBJECTIVE Identify the influence of mesenchymal stem cell (MSC) therapy on peripheral tissue glucose utilization following a myocardial infarction (MI) and dietary‐induced insulin resistance (IR). METHODS C57BL6 mice were high‐fat fed (HFF) for eight weeks. Mice were then segregated into three groups: HFF‐SHAM mice, HFF‐MI+PBS mice undergoing coronary artery ligation to induce a MI followed by intramyocardial injection of phospho‐buffered saline and the HFF‐MI+MSC group receiving MSCs. HFF groups were age‐matched with chow‐fed mice. RESULTS Five weeks post‐MI, glucose utilization was assessed in the conscious, unrestrained mouse by employing a hyperinsulinemic‐euglycemic (insulin) clamp combined with administration of [14C]‐2‐deoxyglucose. The MSC‐treated, chow‐fed mice displayed elevated glucose uptake in the soleus muscle. High‐fat feeding enhanced the MSC‐effect on insulin sensitivity. Whole body insulin responsiveness was higher in the HFF‐MI+MSC, as indicated by a 1.6‐fold increase in glucose infusion rate compared to HFF‐SHAM mice (n=8–12). Also, tissue‐specific glucose uptake (μg/mg/min) was elevated in the soleus (0.95 vs 1.46; HFF‐SHAM vs. HFF‐MI+MSC), gastrocnemius (0.19 vs 0.27), vastus lateralis (0.11 vs 0.23) and adipose tissue (0.03 vs 0.05). CONCLUSIONS MSC transplantation represents a novel therapy for IR induced by diet and a MI. Funded by CIHR and Killam Trusts.