Differential Effect Of Mesenchymal Stem Cell Therapy On Cardiac Glucose Utilization In The Infarcted Heart Following Chow And High Fat Feeding

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.