| Project/Area Number |
06454372
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Yokohama City University |
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Principal Investigator |
NOGUCHI Yoshikazu Yokohama City University, School of Medicine Assisitant Professor, 医学部, 講師 (50180724)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Shinobu Yokohama City University, School of Medicine, Assistant Professor, 医学部, 講師 (80244424)
ITO Takaaki Yokohama City University, School of Medicine, Associate Professor, 医学部, 助教授 (70168392)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1995: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | glucose transporters / insulin resistance / glucose clamp / グルコース クランプ / インスリン レジスタンス / グルコース トランスポーター / グリコース クランプ |
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| Research Abstract |
Cancer cells have been known to have increased rates of glucose metabolism compared with healthy cells. In normal tissue, glucose transporters translocate from the intracytoplasmic domain to the cell membrane to actively transport glucose into cells, however, the function and mechanisms of these transporters in the cancer cells are not clarified yet. This research yielded the following results.
Insulin resistance : More than 80% of the patients with gastrointestinal cancers have insulin resistance of the peripheral tissue. One of the possible mediators of this abnormality may be interleukin (IL) -6, whose serum level is positively correlated with the degree of insulin resistance or M value (glucose metabolised (mg/kg/min) (Submitted). In the cachectic model of Fisher344 rats with methylcholanthrene-induced sarcoma, glucose transporter-4 (Glut-4) in the cytoplasm was significantly decreased quantitatively. Insulin stimulation resulted in smaller amount of the protein to tranlocate to the
… More
cell membrane. This would be on of the major mechanisms of the insulin resistance in the tumor-bearing state.
Glucose transporters : Of 70 cases of gastric cancer, Glut-1 was expressed in 18.5% of the cases, Glut-2 in 20.9%, Glut-3 in 19.4%, Glut-4 in 40.6% and Glut-5 in 5.5%, respectively. Metastatic foci in the regional lymph nodes were also positive for the transporters expressed in the main tumor. Expression of Glut-1 was positively correlated with the degree of lymphatic vessel and blood vessel invasion by _1=0.402, p<0.001 and _1=0.484, p<0.0001. Glut-4 was more frequently stained in the differentiated history than undifferentiated type. Those characteristics in the glucose metabolism was not related with degree of apoptosis or bc1-2 gene product expression in the main tumor (in preparation for submission).
Summary : In gastric cancer specimens insulin responsive glucose transporter (Glut-4) is very frequently expressed irrespective of the presence of the peripheral insulin resistance of the patients. If both of these were examined preoperatively, we may be able to select a subset of the patients who will be benefited by nutritional support without nourishing the tumor. Less
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