Journal Article

Insulin resistance in cavefish as an adaptation to a nutrient-limited environment

Riddle, M.R., Aspiras, A.C., Gaudenz, K., Peuß, R., Sung, J.Y., Martineau, B., Peavey, M., Box, A.C., Tabin, J.A., McGaugh, S., Borowsky, R., Tabin, C.J. and Rohner, N.

Record Number:
3785
Year:
2018
Journal:
Nature
Pages:
647-651
Volume:
555
Abstract:
Periodic food shortages are a major challenge faced by organisms in natural habitats. Cave-dwelling animals must withstand long periods of nutrient deprivation, as—in the absence of photosynthesis—caves depend on external energy sources such as seasonal floods1. Here we show that cave-adapted populations of the Mexican tetra, Astyanax mexicanus, have dysregulated blood glucose homeostasis and are insulin-resistant compared to riveradapted populations. We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia. Hybrid fish from surface–cave crosses carrying this mutation weigh more than non-carriers, and zebrafish genetically engineered to carry the mutation have increased body weight and insulin resistance. Higher body weight may be advantageous in caves as a strategy to cope with an infrequent food supply. In humans, the identical mutation in the insulin receptor leads to a severe form of insulin resistance and reduced lifespan. However, cavefish have a similar lifespan to surface fish and do not accumulate the advanced glycation end-products in the blood that are typically associated with the progression of diabetes-associated pathologies. Our findings suggest that diminished insulin signalling is beneficial in a nutrient-limited environment and that cavefish may have acquired compensatory mechanisms that enable them to circumvent the typical negative effects associated with failure to regulate blood glucose levels.
Times Cited:
1
Related Records:
Hubbs, C.L. and Innes, W.T. (1936)Bridges, W. (1940)Gresser, E. B. and Breder, C. M. (1940)Breder, C. M. and Gresser, E. B. (1941)Breder, C. M. and Gresser, E. B. (1941)Breder, C. M. and Gresser, E. B. (1941)Breder, C. M. (1942)Breder, C. M. (1943)Breder, C. M. (1943)Osorio Tafall, B. F. (1943)Breder, C. M. (1944)Alvarez, J. (1946)Breder, C. M. and Rasquin, P. (1947)Schlagel, S. R. and Breder, C. M. (1947)Alvarez, J. (1947)Breder, C. M. and Rasquin, P. (1947)Rasquin, P. (1949)Luling, K. H. (1953)Luling, K. H. (1953)Luling, K. H. (1953)Thines, G. (1954)Stefanelli, A. (1954)Rasquin, P. and Rosenbloom, L. (1954)Luling, K. H. (1954)Luling, K. H. (1954)Stefanelli, A. (1954)Luling, K. H. (1955)Luling, K. H. (1955)Sadoglu, P. (1956)Sadoglu, P. (1957)Thines, G. and Kahling, J. (1957)Sadoglu, P. (1957)Cahn, P. H. (1958)Grobbel, G. and Hahn, G. (1958)Kahling, J. (1961)Luling, K. H. (1962)Burgers, A. C. J., Bennink, P. J. H. and van Oordt, G. J. (1963)Franck, A. (1964)Thines, G., Wolff-Van Ermengem, F., Boucquey, C. and Soffie, M. (1965)Boucquey, C., Thines, G. and Van Der Borght, C. (1965)Carmignani, M. P. A. (1966)Peters, N. and Peters, G. (1966)Thines, G., Soffie, M. and Vandenbussche, E. (1966)Cavicchioli, G. and Guarnieri, P. (1966)Reed, M. (1966)Sadoglu, P. (1967)Schemmel, C. (1967)Pfeiffer, W. (1967)Pfeiffer, W. (1967)Popper, A. N. and Tavolga, W. N. (1967)Walters, V. and Liu, R. K. (1967)Carmignani, M. P. A. (1968)Wilkens, H. (1968)Mattheij, J. A. (1968)Mattheij, J. A. (1968)Mattheij, J. A. and Sprangers, J. A. P. (1969)Sadoglu, P. and McKee, A. (1969)Weiss, B. A. (1969)Mattheij, J. A. (1969)Mattheij, J. A. (1970)Mattheij, J. A. (1970)Popper, A. N. (1970)Gertychowa, R. (1970)Gertychowa, R. (1970)Weiss, B. and Martini, J. (1970)Whitt, G. S. and Maeda, F. S. (1970)Wilkens, H. (1970)Wilkens, H. (1970)Wilkens, H. (1970)Popper, A. N. (1971)Gertychowa, R. (1971)Wiley, S. and Mitchell, R. W. (1971)Wiley, S. and Mitchell, R. W. (1971)Wilkens, H. (1971)Zaccone, G. (1971)Wilkens, H. and Burns, R. J. (1972)Thines, G. and Wissocq, N. (1972)Avise, J. C. and Selander, R. K. (1972)Wilkens, H. (1972)Wilkens, H. (1972)Wilkens, H. (1972)Zaccone, G. (1972)Zeitlin, S. M. (1973)Zeitlin, S. M. and McDevitt, D. S. (1973)Thines, G. and LeGrain, J. M. (1973)Schemmel, C. (1973)Voneida, T. J. (1973)Durand, J. P. (1973)Yasuda, K. (1973)Mitchell, R. W. (1973)Schemmel, C. (1974)Schemmel, C. (1974)Chakraborty, R. and Nei, M. (1974)Sligar, C. (1974)Sadoglu, P. (1975)Peters, N., Scholl, A. and Wilkens, H. (1975)Omura, Y. (1975)Voneida, T. J. and Sligar, C. (1976)Sligar, C. and Voneida, T. J. (1976)Herwig, H. J. (1976)Durand, J. P. (1976)Herwig, H. J. (1976)Erckens, W. and Weber, F. (1976)Wilkens, H. (1976)Wilkens, H. (1977)Zaccone, G. (1977)Kirby, R. F., Thompson, K. W. and Hubbs, C. (1977)Yew, D. T. and Yoshihara, H. M. (1977)Mitchell, R. W., Russell, W. H. and Elliott, W. R. (1977)Thines, G. and Weyers, M. (1978)Durand, J. P. (1978)Sadoglu, P. (1979)Wilkens, H., Peters, H. and Schemmel, C. (1979)Woodhead, A. D. and Achey, P. M. (1979)Durand, J. P. (1979)Wilkens, H. (1980)Wilkens, H. (1980)Schemmel, C. (1980)Quinn, T. P. (1980)Weissert, R. (1980)Campenhausen, C., Riess, I. and Weissert, R. (1981)Reddell, J. R. (1981)Weissert, R. and Campenhausen, C. (1981)Herwig, H. J. (1981)Jankowska, M. and Thines, G. (1982)Lamprecht, G. and Weber, F. (1982)Erckens, W. and Martin, W. (1982)Erckens, W. and Martin, W. (1982)Rose, F. L. and Mitchell, R. W. (1982)Tabata, M. (1982)Parzefall, J. (1983)Zilles, K., Tillmann, B. and Bennemann, R. (1983)Romero, A. (1983)Wilkens, H. (1984)Voneida, T. J. and Fish, S. E. (1984)Schuppa, M. (1984)Romero, A. (1984)Romero, A. (1984)Teyke, T. (1985)Burchards, H., Dolle, A. and Parzefall, J. (1985)Wilkens, H. (1985)Lamprecht, G. and Weber, F. (1985)Romero, A. (1985)Parzefall, J. (1986)Wilkens, H. (1986)Wilkens, H. and Huppop, K. (1986)De Fraipont, M. (1986)Fraipont, M. (1986)De Fraipont, M. and Thines, G. (1986)Hassan, E. S. (1986)De Fraipont, M. and Thines, G. (1986)Huppop, K. (1986)Romero, A. (1986)Wilkens, H. (1987)De Fraipont, M. (1987)De Fraipont, M. (1987)Huppop, K. (1987)Teyke, T. (1988)Wilkens, H. (1988)Fricke, D. (1988)De Fraipont, M. (1988)Huppop, K. (1988)Teyke, T. (1989)Langecker, T. G. (1989)Fricke, D. and Parzefall, J. (1989)Hassan, E. S. (1989)Huppop, K. (1989)Fack, H. and Wilkens, H. (1989)Teyke, T. (1990)Parzefall, J. and Fricke, D. (1990)Klimpel, B. and Parzefall, J. (1990)Peters, N., Schmidt, W. and Fricke, D. (1990)Abdel-Latif, H., Hassan, E. S. and von Campenhausen, C. (1990)Langecker, T. G. (1990)Yokoyama, R. and Yokoyama, S. (1990)Yokoyama, R and Yokoyama, S (1990)Huppop, K. (1991)Campenhausen, C. (1991)Parzefall, J. and Fricke, D. (1991)Langecker, T. G., Wilkens, H. and Junge, P. (1991)Riedel, G. and Krug, L. (1991)Huppop, K. and Wilkens, H. (1991)Parzefall, J. (1992)Parzefall, J. (1992)Wilkens, H. (1992)Lamprecht, G. and Weber, F. (1992)Wilkens, H. and Meyer, M. (1992)Langecker, T. G. and Longley, G. (1992)De Fraipont, M. (1992)Hassan, E. S., Abdel-Latif, H. and Biebricher, R. (1992)Parzefall, J. (1993)Peters, N., Schacht, V., Schmidt, W. and Wilkens, H. (1993)Langecker, T. G. (1993)Langecker, T. G., Schmale, H. and Wilkens, H. (1993)Langecker, T. G., Schmale, H. and Wilkens, H. (1993)Hoffman, S. and Hausberg, C. (1993)Teyke, T. and Schaerer, S. (1994)Borowsky, R. (1994)Langecker, T. G., Neumann, B., Hausberg, C. and Parzefall, J. (1995)Langecker, T. G., Wilkens, H. and Schmale, H. (1995)Yokoyama, S., Meany, A., Wilkens, H. and Yokoyama, R. (1995)Borowsky, R. (1996)Behrens, M., Langecker, T. G., Wilkens, H. and Schmale, H. (1997)Riedel, G. (1997)Riedel, G. and Krug, L. (1997)Borowsky, R. and Espinasa, L. (1997)Jeffery, WR and Martasian, DP (1998)Wilkens, H. (1998)Contreras-Balderas, S. and Lozano-Vilano, M.D.L. (1998)Behrens, M, Wilkens, H and Schmale, H (1998)Kullander, S. O. (1999)Baker, CF and Montgomery, J (1999)Jeffery, W. R., Strickler, A.G., Guiney, S., Heyser, D.G. and Tomarev, S.I. (2000)Yamamoto, Y. and Jeffery, W. R. (2000)Espinasa, L. and Borowsky, R. (2000)Ford, D.C. (2000)Jeffery, W. R. (2001)Boudriot, F and Reutter, K (2001)Montgomery, J.C., Coombs, S. and Baker, C.F. (2001)Strickler, A.G., Yamamoto, Y. and Jeffery, W. R. (2001)Espinasa, L. and Borowsky, R. (2001)Krejca, J. (2002)Berg, A and Watson, GM (2002)Dowling, TE, Martasian, DP and Jeffery, WR (2002)Romero, A., Jeffery, W.R. and Yamamoto, Y. (2002)Borowsky, RL and Wilkens, H (2002)Strickler, AG, Famuditimi, K and Jeffery, WR (2002)Sarma, SSS, Lopez-Romulo, A and Nandini, S (2003)Porter, M.L. and Crandall, K.A. (2003)Contreras-Balderas, S, Almada-Villela, P, Lozano-Vilano, M de L and Garcia-Ramirez, ME (2003)Wilkens, H. and Strecker, U. (2003)Strecker, U. (2003)Strecker, U., Bernatchez, L. and Wilkens, H. (2003)McCauley, DW, Hixon, E and Jeffery, WR (2004)Protas ME, Hersey C, Kochanek D, Zhou Y, Wilkens H, Jeffery WR, Zon LI, Borowsky R, Tabin CJ. (2006)Protas, M., Conrad, M., Gross, J.B., Tabin, C. and Borowsky, R.L. (2007)Protas, M, Tabansky, I, Conrad, M, Gross, JB, Vidal, O, Tabin, C and Borowsky, RL (2008)Gross, JB, Protas, M, Conrad, M, Scheid, PE, Vidal, O and others (2008)Jeffery, WR (2009)Kowalko, J, Gross, JB, Protas, M, Borowsky, RL and Tabin, C (2009)Kowalko, J, Rohner, N, Borowsky, RL and Tabin, C (2011)Bradic, M, Beerli, P and Borowsky, RL (2011)Esquivel-Bobadilla, S (2011)Wilkens, H. (2012)Trontelj, P. (2012)Jeffery, W.R. (2012)Protas, M. and Jeffery, W. R. (2012)Gross, J.B. (2012)Bradic, M., Beerli, P., Garcia-de Leon, F. J., Esquivel-Bobadilla, S. and Borowsky, R. L. (2012)Kowalko, J. E., Rohner, N., Rompani, S. B., Peterson, B. K., Linden, T. A., Yoshizawa, M., Kay, E. H., Weber, J., Hoekstra, H. E., Jeffery, W. R., Borowsky, R. and Tabin, C. J. (2013)Rohner, N., Jarosz, D. F., Kowalko, J. E., Yoshizawa, M., Jeffery, W. R., Borowsky, R. L., Lindquist, S. and Tabin, C. J. (2013)Rohner, N (2013)Kowalko, J., Rohner, N., Linden, T.A., Rompani SB, Warren, W.C., Borowsky, R, Tabin, C.J., Jeffery, W.R. and Yoshizawa M. (2013)Gross, J.B., Furterer, A., Carlson, B.M. and Stahl, B.A. (2013)Elliott, William R. (2013)Stahl, B. A. and Gross, J. B. (2013)Stahl, AL (2013)Bradic, M., Teotonio, H. and Borowsky, R. L. (2013)Bibliowicz, J., Alie, A., Espinasa, L., Yoshizawa, M., Blin, M., Hinaux, H., Legendre, L., Pere, S. and Retaux, S. (2013)Pazza, R (2013)Moran, D, Softley, R and Warrant, EJ (2014)Espinasa, L., Bartolo, N.D. and Newkirk, C.E. (2014)McGaugh, S.E., Gross, J.B., Aken, B., Blin, M., Borowsky, R., Chalopin, D., Hinaux, H., Jeffery, W.R., Keene, A., Ma, L., Minx, P., Murphy, D., O'Quin, K.E., Retaux, S., Rohner, N., Searl, S.M., Stahl, B.A., Tabin, C., Volff, J.N., Yoshizawa M, Warren WC. (2014)Elliott, W.R. (2014)Silva, D. M. Z. 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(2016)Casane, D and Retaux, S (2016)Beale, A., Whitmore, D and Moran, D (2016)Schmitter-Soto, JJ (2016)O'Quin, Kelly and McGaugh, Suzanne E. (2016)Gross, J.B., Stahl, B.A., Powers, A.K. and Carlson, B.M. (2016)Rohner, Nicolas (2016)Aspiras, A., Tabin, C. and Rohner, N. (2016)Retaux, Sylvie, Alie, Alexandre, Blin, Maryline, Devos, Lucie, Elipot, Yannick and Hinaux, Helene (2016)Wilkens, H. and Strecker, U. (2017)Fumey J, Hinaux H, Noirot C, Thermes C, Re´ taux S, Casane D. (2017)Schmitter-Soto, JJ (2017)Jaggard, J. B., Robinson, B. G., Stahl, B, Oh, I, Masek, P, Yoshizawa, M and Keene, A. (2017)Stahl, B (2017)Stahl, B.A. and Gross, J.B. (2017)Jaggard, J. B. (2017)Krishnan, J and Rohner, N (2017)Alvarado, C.G. (2017)Hinaux, H, Recher, G, Alie, A., Legendre, L, Blin, M. and Retaux, S (2017)Pazza, R., Dergam, J.A. and Kavalco, K.F. (2018)Elliott, W.R. (2018)Devitsina, G.V. and Golovkina, T.V. (2018)Kling, J. (2018)Chin, J.S.R., Gassant, C.E., Amaral, P.M., Lloyd, E., Stahl, B.A., Jaggarda, J.B., Keenea, A.C. and Duboue, E.R. (2018)Fumey, J., Hinaux, H., Noirot, C., Thermes, C., Rétaux, S. and Casane, D. (2018)Stern, D.B and Crandall, K.A. (2018)Xiong, S., Krishnan, J., Peuß, F. and Rohner, N. (2018)Gross, J.B., Weagley, J., Stahl, B.A., Ma, L., Espinasa, L. and McGaugh, S.E. (2018)Espinasa, L. (2018)Espinasa, L., Legendre, L., Fumey, J., Blin, M., Rétaux, S. and Espinasa, M. (2018)Mirande, J.M. (2018)Borowsky, R. (2018)Jaggard, J.B., Stahl, B.A., Lloyd, E., Prober, D.A., Duboue, E.R. and Keene, A.C. (2018)Tabin, J.A., Aspiras, A., Martineau, B., Riddle, M., Kowalko, J. Borowsky, R. Rohner, N. and Tabin, C.J. (2018)Borowsky, R., Luk, A., He, X.J. and Kim, R.S. (2018)Riddle, M.R., Aspiras, A.C., Gaudenz, K., Peuß, R., Sung, J.Y., Martineau, B., Peavey, M., Box, A.C., Tabin, J.A., McGaugh, S., Borowsky, R., Tabin, C.J. and Rohner, N. (2018)Rohner, N. (2018)Garita-Alvarado, C.A., Barluenga, M. and Ornelas-García, C.P. (2018)Alie, A., Devos, L., Torres-Paz, J., Prunier, L., Boulet, F., Blin, M., Elipot, Y. and Retaux, S. (2018)