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

Citation

Material Information

Title:
Insulin resistance in cavefish as an adaptation to a nutrient-limited environment
Series Title:
Nature
Creator:
Riddle, Misty R.
Aspiras, Ariel C.
Gaudenz, Karin
Sung, Jenny Y.
Martineau, Brian
Peavey, Megan
Box, Andrew C. et al
Publisher:
Nature
Publication Date:
Language:
English

Subjects

Subjects / Keywords:
Ecophysiology ( local )
Evolutionary Genetics ( local )
Genre:
serial ( sobekcm )

Notes

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 river-adapted 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.
Original Version:
Nature, Vol. 555 (2018-03-21).

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