Increased Secretion Of ANP In Rat Myocardium May Cause Insulin Resistance

In this century, our country’s aerospace activities have made remarkableachievements. Besides rapid development, it also faces many urgent medical problems.The changes of muscles, bones and circulatory system are particularly obvious duringspace flight. Long-term weightlessness induces atrophy in anti-gravity skeletal muscle,bone loss, changes in structure and function of heart, and a decrease in blood volume.These changes will seriously affect manned space activities, also threaten the health andwork ability of astronauts. Although a lot of researches have been done to study thesechanges in the heart during space flight, but there is still lack of common results aboutANP concentration in plasma and the heart. Both ANP-containing vesicles andGLUT4-containing vesicles need the participation and regulation of SNARE proteinfamily in transportation. There is no report about whether the change of ANP secretion has influence on glucose transportation or not. Therefore, the study of ANP secretion inweightlessness heart and its influence on glucose transportation has certain value inaerospace medicine, and also has certain reference value for the prevention and treatmentof clinical diseases such as diabetes.In the present study, we observed the changes of ANP secretion in4-weektail-suspended rats (SUS) and20-week transverse abdominal aortic constriction rats(TAC), and also observed the expression of related SNARE proteins, the changes ofinsulin sensitivity in vivo, the changes of heart’s glucose uptake in vitro, and theco-localization among ANP, GLUT4and related SNARE proteins at the cell level. Themain results of this study are as follows:1The changes of insulin sensitivity in the SUS and TAC groupsBoth SUS and TAC rats showed a lower glucose infusion rates (GIR) compared withtheir synchronous control rats (CON), so the insulin sensitivity of these two models weredecreased.2The changes of myocardial glucose uptake in the SUS and TAC groupsCardiac glucose standardized uptake value (SUV) showed a significant decrease inthe SUS group compared with the CON group. After insulin treatment, cardiac glucoseSUV also showed a significant decrease in the SUS group compared with the CON group.These results showed that the heart’s ability of glucose uptake with and without insulintreatment was decreased in the SUS group. These results suggested that insulin sensitivitydecreased in the SUS group. Cardiac glucose standardized uptake values (SUV) with andwithout insulin treatment showed the significant decrease in the TAC group comparedwith the CON group. These results suggested that the glucose uptake in the TAC ratmyocardium was lower than that in the CON rat.3ANP secretion and SNARE proteins expression in the SUS and TAC ratmyocardiumANP expression of atrial myocardium showed an increase in the SUS groupcompared with the CON group. ANP showed a slight expression in left ventricularmyocardium of the control rat, but was dectable in the SUS group. Expression of VAMP-1/2(vesicle associated SNARE) increased significantly both in atrial and leftventricular myocardium in the SUS group. Expression of SNAP-23showed an increase inatrial myocardium of the SUS. Synip and Munc-18c as regulators of SNAREs did notshow significant difference between the CON and SUS groups.ANP expression of atrial myocardium showed an increase in the TAC groupcompared with the CON group, and left ventricular myocardium also found expression ofANP. Expression of VAMP-1/2increased significantly both in atrial and left ventricularmyocardium in the TAC group. Expression of SNAP-23showed an increase in atrialmyocardium of the TAC group. Synip and Munc-18c did not show significant differencebetween the CON and TAC groups.4The localization of ANP, GLUT4and SNARE proteins in SUS and TAC ratcardiomyocytesBoth VAMP-1/-2and Syntaxin-4had a co-localization with ANP in cardiomyocytesfrom CON and SUS rats, and the co-localization significantly increased in the SUS groupcompared with the CON group. Both VAMP-1/-2and Syntaxin-4had a co-localizationwith GLUT4in cardiomyocytes from CON and SUS rats, and the co-localizationdecreased in the SUS group compared with the CON group. ANP had no co-localizationwith GLUT4in cardiomyocytes from CON and SUS rats.Both VAMP-1/-2and Syntaxin-4had a co-localization with ANP in cardiomyocytesfrom TAC rats, and the co-localization significantly increased in the TAC group comparedwith the CON group. Both VAMP-1/-2and Syntaxin-4had a co-localization with GLUT4,and the co-localization decreased in the TAC group. ANP had no co-localization withGLUT4in CON and TAC groups.In conclusion, these above results suggest that ANP-containing vesicles andGLUT4-containing vesicles combine competitively with VAMP-1/-2. ANP-containingvesicles may occupy more VAMP-1/-2than GLUT4-containing vesicles because theincrease of ANP secretion in left ventricle of tail-suspended and hypertensive rats. Thesedecrease glucose transport efficiency and then induce cardic insulin resistance in SUS andTAC rats.