| Budget Amount *help |
¥32,500,000 (Direct Cost: ¥32,500,000)
Fiscal Year 1997: ¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 1996: ¥18,200,000 (Direct Cost: ¥18,200,000)
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| Research Abstract |
PI 3-kinases were found to have an important roles to transduce metabolic effects of insulin. However, downstream effectors of P1 3-kinases and their signaling mechanisms were unknown. To elucidate these mechanisms, we expressed several mutants of Akt and atypical PKC in 3T3-Li adipocytes using adenovirus vectors. We found that two serine/threonine kinases, Akt (PKB) and atypical PKC are downstream effectors of P1 3-kinases in 3T3-L1 adipocytes. That is, Akt involved in insulin-stimulated protein synthesis, but not in insulin-stimulated glucose transport. On the other hand, atypical PKC is involved in insulin-stimulated glucose transport, but not in insulin-stimulated protein synthesis. Furthermore, we found that Akt and atypical PKC acts independently in the downstream of P1 3-kinases.
GLUT4-containg vesicles translocates from intracellular compartments to plasma membranes in response to the insulin. However, mechanisms of this translocation were unknown. According to the SNARE hypothesis, we analysed the fusion process of GLUT4-containg vesicles with plasma membrane in 3T3-Ll adipocytes. We found that the binding of VAMP2 in GLUT4-containg vesicles with syntaxin 4 in the plasma membrane is important for the fusion process and the association of Munc 18c with syntaxin 4 prevents the binding of syntaxin 4 with VAMP2.
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