A. The echocar-diogram of WT and db/ db mice. B. The percentage fractional shortening. C. Bar graph of the echocardiogram of db/db and WT representative as bar graph in comparing the chamber dilation (LVIDd and LVIDs) and wall thickness (LVPWd and LVPWs). *p<0.05, n=6. D. (i): Western blotting of the heart tissue from WT (C57BL/6J) and db/db mice. GAPDH is used as a loading control. (ii). Representative bar graph with densitometry analysis. **p<0.01, n = 6. E. (i). Co-localization of homocys-teine (red color) and Gs (green color) in db/db and WT cardiomyocytes. (ii). Bar graph for fluorescent intensity. Arbitrary unit (a.u) *p<0.01, n=5.

A. The ratio of the heart weight to body weight in the four groups of db/db mice. *p<0.05, n=6. B. (i): Representative echocardiograms of the four groups: db/db (DB), DB+ salbutamol (DBS), DB+ exercise (DBE), DB+ salbutamol + exercise (DBES). (ii): The percentage fractional shortening of the above four groups. *p<0.05, n=6. C. Comparison of left ventricle internal dimension in systole (LVIDs) among the four groups: DB, DBS. DBE and DBES. *p<0.05, n=6. D. The time required to the 90% peak height during systolic contraction of cardiomyocytes among the four groups: *p<0.05, n=6. E. (i): A representative graph for the calcium transient of cardiomyocytes from the four groups, (ii): The bar graph in the left panel shows the calcium consumption during baseline to peak height. *p<0.05; **, p< 0.01, n=6. F. (i): A representative RT-PCR forSERCA2 mRNA expression among the four groups. The 18s is used for normalization. (ii): The bar graph showing the relative expression of SERCA2 among the four groups. *p<0.05, n=5. G. (i): A representative RT-PCR showing mRNA expression of β2-AR among the four groups. (ii): The bar graph showing the relative expression of β2-AR among the four groups. *p<0.05, ** p<0.01, *** p<0.001, n=5. H. (i): A representative Western blots showing expression of β2-AR protein among the four groups. (ii): The bar graph showing relative expression of β2-AR protein among the four groups. *p<0.05, ** p<0.01, *** p<0.001, n=5. I. (i): Co-immunoprecipitation of Hcy with β2-AR using the heart tissue from the four groups. (ii): The bar graph represents the relative expression of Hcy among the four groups. *p<0.05, ** p< 0.01, n=5.

A. (i): Western blotting showing expression of β-AR in HL1 cardiomyo-cytes treated with high dose of sucrose. GAPDH is a loading control, (ii): The scanned unit of bands is shown in the left panel. *p<0.05, n=4. B. (i): Flow cytometry of HL1 cardiomyocytes treated with h o m ocyste i n e (100μM). (ii): The gated population is analyzed for the β2-AR stained cell counts. *p<0.01, n= 4.

A schematic representation of the effect of exercise on contractile dysfunction in diabetes. The impairment of contractility is due, in part, to the attenuation of β2-AR response caused by inhibition of Gs and up regulation of homocysteine. Exercise lowers homocysteine level, induces Gs, restores β2-AR response and mitigates contractile dysfunction.