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Nature. 2018 Mar 29;555(7698):647-651. doi: 10.1038/nature26136. Epub 2018 Mar 21.

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

Author information

1
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
2
Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.
3
College of Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108, USA.
4
Department of Biology, New York University, New York, New York 10003, USA.
5
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

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 floods. 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.

PMID:
29562229
PMCID:
PMC5989729
DOI:
10.1038/nature26136
[Indexed for MEDLINE]
Free PMC Article

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