Restoration of myocardial glucose uptake with facilitated myocardial glucose transporter 4 translocation contributes to alleviation of diabetic cardiomyopathy in rats after duodenal‐jejunal bypass

Figures

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  Figure 1. Evaluation of cardiac function in the control and diabetic groups before the surgery. (a) Representative M‐mode (left), pulsed‐wave Doppler mode (middle) and tissue Doppler mode (right) echocardiogram along with measurements of left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), peak velocities of early filling (E) and peak early diastolic velocities (e′). (b–g) Sequential evaluations of (b) heart rate, (c) LVEDD, (d) LVESD, (e) ejection fraction (EF), (f) fractional shortening (FS) and (g) E/e′. Data are expressed as mean ± standard deviation. n = 10 in the control group and n = 20 in the diabetic group. *P < 0.05, **P < 0.01 diabetic versus control.

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  Figure 2. Bodyweight, food intake and glucose homeostasis of rats. (a) Bodyweight, (b) food intake, (c) fasting plasma glucose (FPG), (d) fasting insulin (FINS) and (e) homeostasis model assessment of basal insulin resistance (HOMA‐IR) before and after surgery. (f) The area under the curve (AUC) for the oral glucose tolerance test and (AUCOGTT) and (g) insulin tolerance test (AUCITT) before and at 2 and 8 weeks after surgery. (h) Level of plasma glucagon‐like peptide‐1 (GLP‐1) before and at 2 and 8 weeks after surgery. Data are expressed as mean ± standard deviation for n = 10 per groups. A P, difference by groups; B P, difference over time; C P, difference due to interaction of groups and time in two‐way anova. *P < 0.05, **P < 0.01 sham versus control; ## P < 0.01 duodenal‐jejunal bypass versus sham; & P < 0.05, && P < 0.01 duodenal‐jejunal bypass versus control.

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  Figure 3. Effect of duodenal‐jejunal bypass (DJB) on diabetes‐induced cardiac remodeling. (a) Representative (a1) longitudinal and (a2) transverse sections of left ventricle stained with hematoxylin–eosin. Scale bar, 50 μm. (b1) Interstitial (scale bar, 100 μm) and (b2) perivascular (scale bar, 50 μm) fibrosis, as shown by Masson's trichrome stain. Collagen fibers are dark blue and myocardium is red. (c) Representative Oil Red O‐stained myocardial sections, the red droplets indicate neutral lipid staining. Scale bar, 20 μm. (d) Representative immunohistochemical images of (d1) collagen I and (d2) III. Brown staining is considered positive. Scale bar, 100 μm. (e) Representative transmission electron micrographs images of left ventricle tissues, the blue triangles indicate lipid droplets. Scale bar, 2 μm (magnification, ×10,000) (f) The myocyte size of the three groups. (g) The collagen volume fraction (CVF) of the three groups. (h) The perivascular collagen area/luminal area ratio (PVCA/LA) ratio of the three groups. (i) Semi‐quantification of collagen I and III staining indicated by integrated optical density/area relative density, the value of the control group was used as the standard…

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  Figure 4. Effect of duodenal‐jejunal bypass (DJB) on cardiac function and myocardial glucose uptake. (a–e) Sequential evaluations of (a) left ventricular end diastolic diameter (LVEDD), (b) left ventricular end systolic diameter (LVESD), (c) ejection fraction (EF), (d) fractional shortening (FS) and (e) the ratio peak velocities of early filling/peak early diastolic velocities of (E/e′) at 8 weeks after surgery. (f) Result of hemodynamic measurement indicated by left ventricular end diastolic pressure (LVEDP). (g) Representative transverse axis images of the heart showing 18F‐FDG distribution in the first (g1), second (g2), and third (g3) rounds of PET scan, the yellow cross indicates the position of heart. (h) Representative three‐dimensional reconstruction of the third round of fluorine‐18 labeled fluorodeoxyglucose scan, the green square indicates the position of the heart. The first round was carried out regularly after fluorine‐18 labeled fluorodeoxyglucose injection, whereas the second round was carried out after an intravenous glucose load, and the third round was carried out after an intragastric glucose load. (i) The statistical results of standard uptake value (SUV). Data are…

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  Figure 5. Impact of duodenal‐jejunal bypass (DJB) on myocardial glucose and fatty acid transporter. (a) Representative immunohistochemical staining of glucose transporter 4 (GLUT‐4) in (a1) longitudinal (scale bar, 100 μm) and (a2) transverse (scale bar, 50 μm) myocardial sections. Brown staining is considered positive. (b) Representative western blot of myocardial total and plasma membrane GLUT‐1 and GLUT‐4. (c) Representative western blot of myocardial total and plasma membrane CD36. (d–f) Comparisons of (d) total expression, (e) plasma membrane expression, and (f) membrane/total ratio of GLUT‐1, GLUT‐4 and cluster of differentiation 36 (CD36), the value of control group was used as standard (100%). Data are expressed as mean ± standard deviation for n = 10 per groups. **P < 0.01 sham versus control; # P < 0.05, ## P < 0.01 DJB versus sham.

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  Figure 6. Impact of duodenal‐jejunal bypass (DJB) on myocardial expression of proteins involved in insulin signaling and glucose transporter 4 (GLUT‐4) translocation. (a) Representative western blot of proteins in myocardial insulin signaling pathway. (b–d) Comparisons of (b) phospho/total ratio of insulin receptor substrate 1 (IRS1), (c) phosphatidylinositol 3‐kinase (PI3K) and (d) protein kinase B (AKT). (e, f) Representative western blot of proteins involved in GLUT‐4 translocation. (g) Comparisons of phospho/total ratio of AKT substrate of 160 kDa (AS160). (h) Comparisons of phospho/total ratio of TBC1D1. (i) Comparisons of vesicle associated membrane protein 2 (VAMP2), synaptosome‐associated protein of 23 kDa (SNAP23) and syntaxin 4 expression, the value of the control group was used as the standard (100%). Data are expressed as mean ± standard deviation for n = 10 per groups. ** P < 0.01 sham versus control; # P < 0.05, ## P < 0.01 DJB versus sham; & P < 0.05 DJB versus control.