Insulin action in intact mouse diaphragm I.
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Summary
The incubation of intact mouse diaphragms with insulin caused a dose and time dependent increase in the independent activity of glycogen synthase in tissue extracts. 2-deoxyglucose (2–10 mm) alone markedly stimulated the conversion of glycogen synthase to the independent activity under conditions in which tissue ATP concentrations were not affected. The incubation of diaphragms with both insulin and 2-deoxyglucose resulted in a greater than additive effect. Insulin stimulated the uptake of 2-deoxyglucose into mouse diaphragms, accumulating as 2-deoxyglucose-6-phosphate. The accumulation of 2-deoxyglucose-6-phosphate correlated well with the increase in the independent activity of glycogen synthase and with the activation of glycogen synthase phosphatase in tissue extracts. The uptake of 3-0-methyl glucose was also markedly stimulated by insulin, without affecting the activity of glycogen synthase. Both glucose-6-phosphate and 2-deoxyglucose-6-phosphate stimulated the activation of endogenous glycogen synthase phosphatase activity in muscle homogenates. We conclude that insulin, in addition to its effects in the absence of exogenous sugars, increases the independent activity of glycogen synthase through increased sugar transport resulting in increased concentrations of sugar-phosphates which promote the activity of glycogen synthase phosphatase.
Keywords
Phosphatase Activity Insulin Action Tissue Extract Independent Activity Sugar TransportAbbreviations
- GS
Glycogen synthase
- GS-I
Glycogen synthase activity independent of G6P
- GS-D
Glycogen synthase activity dependent on G6P
- G6P
Glucose-6-phosphate
- ATP
Adenosine triphosphate
- EDTA
Ethylene diamine tetracetic acid
- Mops
Morpholinopropane sulfonic acid
- 2DG
2-Deoxy glucose
- 3-0-MG
3-0-Methyl glucose
- tricine
N-tris(Hydroxymethyl)methyl glycine Enzymes: Glycogen Synthase — UDPGlucose — Glycogen Glucosyl — Transferase (EC 2.4.1.11)
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References
- 1.Lawrence, J. C., Jr. and Larner, J., 1979. J. Biol. Chem. 253, 2104–2113.Google Scholar
- 2.Kipnis, D. M. and Cori, C. F., 1957. J. Biol. Chem. 224, 681.Google Scholar
- 3.Gey, G. O. and Gey, M. K., 1936. Amer. J. Cancer 27, 45–51.Google Scholar
- 4.Thomas, J. A., Schlender, K. K. and Larner, J., 1968. Anal. Biochem. 25, 486–489.Google Scholar
- 5.Oren, Y. and Larner, J., 1979. Anal. Biochem. 94, 409–410.Google Scholar
- 6.Penefsky, H. S., 1977. J. Biol. Chem. 252, 2891–2897.Google Scholar
- 7.Renner, E. D., Plagemann, P. G. W. and Bernlohn, R. W., 1972. J. Biol. Chem. 247, 5765–5776.Google Scholar
- 8.Lowry, O. M., Rosenbrough, N. J., Farr, A. L. and Randall, R. J., 1951. J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
- 9.Williamson, J. R. and Corkey, B. R., 1969. Methods Enzymol. 13, 434.Google Scholar
- 10.Larner, J., Roach, P. J., Huang, L. C., Brooker, G., Murad, F. and Hazen, R., 1979. Hormones and Energy Metabolism (Klachko, D. M., Anderson, R. R. and Heimberg, M., eds.) pp. 103–123. Plenum Press, New York.Google Scholar
- 11.Larner, J., Galasko, G., Cheng, K., DePaoli-Roach, A. A., Huang, L. C., Daggy, P. and Kellogg, J., 1979. Science 206, 1408–1410.Google Scholar
- 12.Miller, T. B. and Larner, J., 1972. Proc. Nat. Acad. Sci. 69, 2774–2777.Google Scholar
- 13.Miller, T. B. and Larner, J. 1973. J. Biol. Chem. 248, 3483–3488.Google Scholar
- 14.Huijing, F., Nuttal, F. Q., Villar-Palasi, C. and Larner, J., 1969. Biochim. Biophys. Acta 177, 204–212.Google Scholar
- 15.Roach, P. J., Takeda, Y. and Larner, J., 1976. J. Biol. Chem. 251, 1913–1919.Google Scholar
- 16.Kipnis, D. M. and Cori, C. F., 1960. J. Biol. Chem. 235, 3070–3075.Google Scholar
- 17.Helmreich, E. and Eisen, H. N., 1959. J. Biol. Chem. 234, 1958–1965.Google Scholar
- 18.Nuttal, F. Q. and Gannon, M. C., 1972. Clin. Res. 20, 777 (abstract).Google Scholar
- 19.Hizukuri, S. and Takeda, Y., 1970. Biochim. Biophys. Acta 211, 179–181.Google Scholar
- 20.Kato, K. and Bishop, J. S., 1972. J. Biol. Chem. 247, 7420–7429.Google Scholar
- 21.Nakai, C. and Thomas, J. A. 1974. J. Biol. Chem. 249, 6459–6467.Google Scholar
- 22.Killilea, S. D., Brandt, H., Lee, E. Y. C. and Whelan, W. J., 1976. J. Biol. Chem. 251, 2363–2368.Google Scholar
- 23.Larner, J., Villar-Palasi, C. and Richman, D. J., 1960. Archives Biochem. Biophys. 86, 56–60.Google Scholar
- 24.Walker, D. G., 1966. Essays in Biochemistry (Campbell, P. N. and Greville, G. D., eds.) Vol. 2, pp. 33–67, Academic Press, New York.Google Scholar
- 25.Ernst, V., Levin, D. H. and London, I. M., 1978. J. Biol. Chem. 253, 7163–7172.Google Scholar
- 26.Ochoa, S. and de Haro, C., 1979. Ann. Rev. Biochem. (Snell, E. E., ed.) Vol. 48, pp. 549–580, Annual Reviews Inc., Palo Alto, USA.Google Scholar
- 27.Brautigan, D. L., Kerrick, W. G. L. and Fischer, E. H., 1980. Proc. Natl. Acad. Sci. USA, 77, 936–939.Google Scholar