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
Relevent Species: