지구성 운동과 셀레니움 투여가 당뇨 Goto-kakizaki 쥐의 골격근의 MCT1과 MCT4단백질 발현수준에 미치는 효과 Effects of Exercise Training and Selenium on MCT1 and MCT4 Protein Levels in Skeletal Muscles of Diabetic Goto-Kakizaki Rats원문보기
이 연구는 지구성 운동과 셀레니움 투여가 Coto-Kakizaki 쥐의 젖산수송 능력에 독립적으로 혹은 상호작용하여 영향을 미치는가를 구명하는데 그 목적이 있다. 실험동물들의 집단은 비교집단(n=10, SED), 지구성 운동집단(n=10, EXER), 셀레니움 투여집단(n=10, SELE)과 지구성 운동과 셀레니움 투여 병행 집단(n=10, COMBI)으로 분류하여 6주간 실험을 실시하였다. 6주간 실험 처치 후 체중은 비교집단에 비해 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 현저하게 감소하였으며 당 부하검사를 실시한 결과에서도 비교집단에 비해 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 90분과 120분 사이에서 혈당 수준이 유의한 낮은 것으로 나타났다. 간 글리코겐 수준은 비교집단과 셀레니움 투여집단에 비해 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 유의하게 높은 것으로 나타났다. 가자미근과 족저근의 글리코겐 수준도 비교집단과 셀레니움 투여집단에 비해 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 현저하게 높은 것으로 나타났다. 혈액 생화학 성분의 경우, 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 고밀도 지단백 수준 증가와 함께 혈장 젖산, 혈청 중성지방, 인슐린, 총 콜레스테롤과 HOMA-IR 수준이 현저하게 감소한 것으로 나타났다. 특히 혈청 중성지방 수준은 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 셀레니움 투여집단에 비해 유의하게 낮은 것으로 나타났다. 이 연구에 가장 중요한 결과는 혈당과 젖산 수송과 관련된 단백질 발현 수준이 6주간의 실험처치 후에 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 가자미근의 MCT1과 미토콘드리아 MCT1 단백질 발현수준이 현저하게 증가하였다는 결과와 함께 가자미근과 족저근의 MCT4 단백질 발현 수준도 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 현저하게 증가하였다는 결과이다. 이러한 결과를 근거로 볼 때 지구성 운동과 셀레니움 투여는 독립적으로 혹은 상호작용하여 혈당과 젖산수송 능력을 개선시키는데 도움이 된다는 것을 알 수 있으며 특히 인슐린 저항 특성과 함께 고젖산혈증을 나타내는 제 II형 당뇨 환자들의 당뇨 처치를 위한 방법으로 활용할 만한 가치가 있는 것으로 생각된다.
이 연구는 지구성 운동과 셀레니움 투여가 Coto-Kakizaki 쥐의 젖산수송 능력에 독립적으로 혹은 상호작용하여 영향을 미치는가를 구명하는데 그 목적이 있다. 실험동물들의 집단은 비교집단(n=10, SED), 지구성 운동집단(n=10, EXER), 셀레니움 투여집단(n=10, SELE)과 지구성 운동과 셀레니움 투여 병행 집단(n=10, COMBI)으로 분류하여 6주간 실험을 실시하였다. 6주간 실험 처치 후 체중은 비교집단에 비해 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 현저하게 감소하였으며 당 부하검사를 실시한 결과에서도 비교집단에 비해 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 90분과 120분 사이에서 혈당 수준이 유의한 낮은 것으로 나타났다. 간 글리코겐 수준은 비교집단과 셀레니움 투여집단에 비해 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 유의하게 높은 것으로 나타났다. 가자미근과 족저근의 글리코겐 수준도 비교집단과 셀레니움 투여집단에 비해 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 현저하게 높은 것으로 나타났다. 혈액 생화학 성분의 경우, 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 고밀도 지단백 수준 증가와 함께 혈장 젖산, 혈청 중성지방, 인슐린, 총 콜레스테롤과 HOMA-IR 수준이 현저하게 감소한 것으로 나타났다. 특히 혈청 중성지방 수준은 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 셀레니움 투여집단에 비해 유의하게 낮은 것으로 나타났다. 이 연구에 가장 중요한 결과는 혈당과 젖산 수송과 관련된 단백질 발현 수준이 6주간의 실험처치 후에 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 가자미근의 MCT1과 미토콘드리아 MCT1 단백질 발현수준이 현저하게 증가하였다는 결과와 함께 가자미근과 족저근의 MCT4 단백질 발현 수준도 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 현저하게 증가하였다는 결과이다. 이러한 결과를 근거로 볼 때 지구성 운동과 셀레니움 투여는 독립적으로 혹은 상호작용하여 혈당과 젖산수송 능력을 개선시키는데 도움이 된다는 것을 알 수 있으며 특히 인슐린 저항 특성과 함께 고젖산혈증을 나타내는 제 II형 당뇨 환자들의 당뇨 처치를 위한 방법으로 활용할 만한 가치가 있는 것으로 생각된다.
The purpose of this study was to determine the possible additive effects of endurance exercise training (EXER) and selenium (SELE) on the improvements of glucose and lactate transport capacities in diabetic Goto-kakizaki rats. Animals either remained sedentary control (SED) or performed EXER or rece...
The purpose of this study was to determine the possible additive effects of endurance exercise training (EXER) and selenium (SELE) on the improvements of glucose and lactate transport capacities in diabetic Goto-kakizaki rats. Animals either remained sedentary control (SED) or performed EXER or received SELE [$5{\mu}mol$ kg body wt (-1) day (-1)], or underwent both EXER and SELE (COMBI), which lasted for 6 wk. Compared with sedentary control, EXER alone or the SELE alone group, or the combined treatment group had significant reduction in glucose response measured at 90 min and 120 min during an intraperitoneal glucose tolerance test (IPGTT) and body weight after 6week treatment. EXER alone, or combined group individually had significantly higher glycogen contents in liver compared with SED or SELE groups. EXER alone increased glycogen content in soleus and plantaris compared with SED, and this parameter was increased to greatest extent in the combined treatment groups compared with SED or SELE groups. EXER alone, SELE alone or COMBI, caused significant decreases in the plasma lactates, serum glucose, insulin, total cholesterol and HOMA-IR along with a significant increase in high-density lipoprotein cholesterol compared with SED. In addition, EXER or COMBI individually had significantly lower serum triacylglycerol compared with SED or SELE. With respect to protein expression related to glucose and lactate transport capacities, EXER alone, SELE alone, or COMBI increased in MCT1 and MCT4 protein level in soleus and plantaris. Furthermore, EXER alone, SELE alone or COMBI caused significant increases in mt MCT1 protein level in soleus and plantaris. The findings of the current study suggest that endurance exercise training and selenium treatment may provide therapeutic values to type II diabetic patients with peripheral insulin resistance and hyperlactatecemia by improving glucose and lactate transport capacities, leading to improvements in plasma lactate, serum glucose, insulin and lipid profiles (TC, TG, HDL).
The purpose of this study was to determine the possible additive effects of endurance exercise training (EXER) and selenium (SELE) on the improvements of glucose and lactate transport capacities in diabetic Goto-kakizaki rats. Animals either remained sedentary control (SED) or performed EXER or received SELE [$5{\mu}mol$ kg body wt (-1) day (-1)], or underwent both EXER and SELE (COMBI), which lasted for 6 wk. Compared with sedentary control, EXER alone or the SELE alone group, or the combined treatment group had significant reduction in glucose response measured at 90 min and 120 min during an intraperitoneal glucose tolerance test (IPGTT) and body weight after 6week treatment. EXER alone, or combined group individually had significantly higher glycogen contents in liver compared with SED or SELE groups. EXER alone increased glycogen content in soleus and plantaris compared with SED, and this parameter was increased to greatest extent in the combined treatment groups compared with SED or SELE groups. EXER alone, SELE alone or COMBI, caused significant decreases in the plasma lactates, serum glucose, insulin, total cholesterol and HOMA-IR along with a significant increase in high-density lipoprotein cholesterol compared with SED. In addition, EXER or COMBI individually had significantly lower serum triacylglycerol compared with SED or SELE. With respect to protein expression related to glucose and lactate transport capacities, EXER alone, SELE alone, or COMBI increased in MCT1 and MCT4 protein level in soleus and plantaris. Furthermore, EXER alone, SELE alone or COMBI caused significant increases in mt MCT1 protein level in soleus and plantaris. The findings of the current study suggest that endurance exercise training and selenium treatment may provide therapeutic values to type II diabetic patients with peripheral insulin resistance and hyperlactatecemia by improving glucose and lactate transport capacities, leading to improvements in plasma lactate, serum glucose, insulin and lipid profiles (TC, TG, HDL).
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제안 방법
Animals in exercise-trained group ran 30 minutes a day at 21 m/min for 5 day/week, at 0% grade for 6 weeks. Prior to the treadmill exercise training, the Goto-Kakisaki rats were allowed a minimum 2 week familiarization peri od to the new environment, consisting of running for 10 min/day on the treadmill (11 m/min).
Muscles with different metabolic properties were selected to study glycogen content, monocarboxylate transporter 1, 4 (MCTs) expression.
대상 데이터
Eight-wk-old male Goto-Kakisaki (GK) rats which are highly inbred strain of wistar rats that sponta neously develop Type II diabetes without obesity (n=40z 280.30±20.35 g) were obtained from Charles River JAPAN (Charles River Japan, Inc, Yokohama) and cared for ac cording to the Guiding Principles for the Care and Use of Animals, based on the Helsinki Declaration of 1964 and were studied from 46 weeks of age (n=26, 336.05±4.13 g) to 52 weeks of age (n=26, 365.16±38.23 g).
데이터처리
All values were expressed as means±SE. A two way ANOVA for repeated measures was used to evaluate statistically sig nificance of IPGTT measured. Student Newman-Keuls post hoc test was the post hoc analysis used to detect difference over time.
Student Newman-Keuls post hoc test was the post hoc analysis used to detect difference over time. When comparing groups, statistical significance was determined by using one-way ANOVA. If a statistically significant difference was observed, Student Newman-Keuls post hoc te마 was used.
성능/효과
In conclusion, we have confirmed that endurance ex ercise training and chronic administration of the anti oxidant selenium individually improve glucose tolerance and induce insulin-like actions on down-regulation of glu cose, TC, TG level and prophylactic effect in the markedly insulin- resistant, diabetic GK rats. Moreover, we have pro vided new evidence that the combination of these inter ventions is associated with greater improvements in skel etal muscle insulin-like action than either intervention individually.
sedentary control). Moreover, The exercise-trained alone, selenium treatment alone or com bined treatment group, caused significant increases in mt MCT1 protein level in soleus (26.7%, 37.1% and 31.0%, re spectively, vs. sedentary control) and plantaris (25.2%, 31.7% and 45.0%, respectively, vs. sedentary control). The exercise-trained alone, SELE-treatment alone or combined treatment group, caused significant increases in MCT4 pro tein level in soleus (31.
sedentary control). The exercise-trained alone, SELE-treatment alone or combined treatment group, caused significant increases in MCT4 pro tein level in soleus (31.6%z 28.3% and 42.5%, respectively, vs. sedentary control) and plantaris (21.7%, 29.7% and 38.2%, respectively, vs. sedentary control).
The plasma lev인 of lactate and the serum levels of glucose, insulin, and lipids in the various groups are shown in table 1. The exercise-trained, selenium treatment and combined treatment groups had significantly lower plasma lactates, serum glucose, insulin, total cholesterol, and HOMA-IR along with a significant increase in high-density lipoprotein cholesterol compared with sedentary controls. Exercise trained or the combined groups individually had significantly lower serum trigly ceride compared with the sedentary control group or sele nium treatment group.
muscle. This study has shown that total and mi tochondrial MCT1Z and total MCT4 protein levels in mus cles are regulated both by the ambient metabolic milieu (glucose, insulin, lactate) and by exercise training. A num ber of studies have already shown that exercise training or altered metabolic demand by muscle regulates MCT ex pression [9, 18].
후속연구
Nevertheless, Whatever the mechanism involved, or as a mentioned previously, it is clear that selenium treatment provided a substantial insulin-like effects on total and mi tochondrial MCT1, and total MCT4 protein levels in in sulin resistant skeletal muscle. Further research is needed to identify the mechanisms underlying the beneficial ef fects on selenium treatment in ameliorating the skeletal muscle insulin resistance of the diabetic GK rat. The results of the present study indicate that improvement in lactate transport in soleus or plantaris muscle is regulated either by the supplemented selenium through insulin-like action on ambient metabolic milieu (glucose, insulin, lactate) or by increased contractile activity (exercise training).
MCT4 protein levels. Further research is needed to identify the mechanisms underlying the beneficial inter action between exercise training and selenium in amelio rating the skeletal muscle insulin resistance of the diabetic GK rat.
참고문헌 (27)
Adamo, K. B. and T. E. Graham. 1998. Comaparison of traditional measurements with macro glycogen and pro-glycogen anna lysis of muscle glycogen. Journal of Applied Physiology 84(3), 908-913.
Becker, D. J., B. Reul, A. T. Ozcelikay, J. P. Buchetm, J. C. Henquin and S. M. Brichard, 1996. Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats. Diabetologia 39(1), 3-11.
Bo, S., A. Lezo, G. Menato, M. L. Gallo, C. Bardelli, A. Signorile, C. Berutti, M. Massobrio and G. F. Pagano. 2005. Gestational hyperglycemia, zinc, selenium, and antioxidant vitamins. Nutrition 21(2), 186-191.
Carey, P. E., J. Halliday, J. E. Snaar, P. G. Morris and R. Taylor. 2003. Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects. American Journal of Physiological Endocrinology Metabolism 284(4), E688-E694.
Enoki, T., Y. Yoshida, H. Hatta and A. Bonen, 2003. Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscle of STZ-induced diabetic rats. Journal of Applied Physiology 94, 2433-2438.
Ferrannini, E., A. Lanfranchi, F. Rohner-Jeanrenaud, G. Manfredini and Van de G. Werve. 1990. Influence of long-term diabetes on liver glycogen metabolism in the rat. Metabolism 39(10), 1082-1088.
Ghosh, R, B. Mukherjee and M. A. Chatterjee. 1994. Novel effect of selenium on streptozotocin-induced diabetic mice. Diabetes Research 25(4), 165-171.
Goodyear, L. J., M. F. Hirshman, R. J. Smith and E. S. Horton. 1991. Glucose transporter number, activity and isoform content in plasma membranes of red and white skeletal muscle. American Journal of Physiology 261, E556-E561.
Goto, Y., M. Kakizaki and N. Masaki. 1976. Production of spontaneous diabetic rats by repetition of selective breeding. Tohoku Journal of Experimental Medicine 119(1), 85-90.
Halestrap, A. P. and N. T. Price. 1999. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochemical Journal 343, 281-299.
Hajduch, E., Heyes, R. R., Watt, P. W. and Hundal, H. S. 1999. Lactate transport in rat adipocyte: identification of monocarboxylate transport 1 (MCT1) and its modulation during streptozotocin-induced diabetes. FEBS Lett. 479, 281-299.
Juel, C. and A. P. Halestrap. 1999. Lactate transport in skeletal muscle-role and regulation of the monocarboxylate transporter. Journal of Physiology 517, 633-642.
Khamaisi, M., R. Potashnik, A. Tirosh, E. Demshchak, A. Rudich, H. Tritschler, K. Wessel and N. Bashan. 1997. Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabe tic rats. Metabolism 46, 763-768.
Metz, L., M. Vermaelen, K. Lambert, C. Broca, P. Sirvent, C. Raynaud and J. Mercier. 2005. Endurance training increases lactate transport in male Zucker falfa rats. Biochemical and Biophysical Research Communications 331, 1338-1345.
Mondon, C. E., I. R. Jones, S. Azhar, C. B. Hollenbeck and G. M. Reaven. 1992. Lactate production and pyruvate dehydrogenase activity in fat skeletal muscle from diabetic rats. Diabetes 41, 1547-1554.
Muller, A. S., E. Most and J. Pallauf. 2005. Effects of a supranutritional dose of selenate compared with selenite on insulin sensitivity in type II diabetic dbdb mice. J. Anim. Physiol. Anim. Nutr. 89(3-6), 94-104.
Mueller, A. S. and J. Pallauf. 2006. Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice. Journal of Nutritional Biochemistry 17(8), 548-560.
Py, G., N. Eydoux, A. Perez-Martin, E. Raynaud, J. F. Brun, C. Prefaut and J. Mercier. 2001. Streptozotocin-induced diabetes decreases rat sarcolemmal lactate transport. Metabolism 50, 418-424.
Py, G., K. Lambert, O. Milhavet, N. Eydoux, C. Prefaut and J. Mercier. 2002. Effect of streprozotocin-induced diabetes in markers of skeletal muscle metabolism and monocarboxylate transporter 1 to monocarboxylate transporter 4 transporters. Metabolism 51, 807-813.
Tan, M. H., A. Bonen, W. Watson-Wright, D. Hood, M. Sopper, D. Currie, A. N. Belcastro and G. Pierce. 1984. Muscle glycogen repletion after exercise in trained normal and diabetic rats. Journal of Applied Physiology 57(5), 1404-1408.
Tan, M. H., A. Bonen, J. B. Garner and A. N. Belcastro. 1982. Physical training in diabetic rats: effect on glucose tolerance and serum lipids. Journal of Applied Physiology 52(6), 1514-8.
Tancrede, G., S. Rousseau-Migneron and A. Nadeau. 1982. Beneficial effects of physical training in rats with a mild streptozotocin-induced diabetes mellitus. Diabetes 31 (5Pt1), 406-409.
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