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Differential effect of mesenchymal stem cell therapy on cardiac glucose utilization in the infarcted heart following chow and high fat feeding
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.386.9
Subject(s) - medicine , endocrinology , insulin resistance , mesenchymal stem cell , ventricle , myocardial infarction , insulin , saline , pathology
OBJECTIVE To determine whether mesenchymal stem cell therapy minimizes abnormal cardiac glucose utilization following a myocardial infarction (MI) in the presence of dietary‐induced insulin resistance. METHODS C57BL6 mice were high fat‐fed (HFF) for eight weeks. Mice were separated into three groups: HFF‐SHAM, HFF‐MI+PBS in which mice were given a MI followed by intramyocardial injection of saline and the HFF‐MI+ MSC group receiving MSCs. HFF groups were age‐matched with chow‐fed mice. RESULTS Five weeks post‐MI, cardiac glucose utilization was evaluated in the conscious, unrestrained mouse by performing a hyperinsulinemic‐euglycemic (insulin) clamp coupled with [14C]‐2‐deoxyglucose administration. In chow‐fed mice, MSCs preserved glucose uptake (μg/mg/min) in the remote left ventricle (RLV) (7.36 vs. 5.16 vs 6.00; CHOWSHAM vs CHOW‐MI+PBS vs CHOW‐MI+MSC). In HFF mice, MSCs increased insulin‐stimulated glucose uptake in the periinfarct region (3.85 vs 3.84 vs 5.24; HFF‐SHAM vs HFF‐MI+ MSC vs HFF‐MI+MSC). RLV glucose uptake in the HFF‐MI+ MSC group was higher than that of the HFF‐MI+PBS mice (4.80 vs 3.38). Immunoblots indicate MSCs preserve insulin signaling (p‐Akt/Akt) in chow‐fed mice. In contrast, this ratio was similar in HFF groups. CONCLUSIONS MSC tberapy promotes insulin sensitivity post‐MI differently in response to a high fat diet. Funded by CIHR and Killam Trusts.