ZFIN ID: ZDB-PUB-180322-13
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., Rohner, N.
Date: 2018
Source: Nature   555(7698): 647-651 (Journal)
Registered Authors: Rohner, Nicolas
Keywords: none
MeSH Terms:
  • Acclimatization/physiology*
  • Aging/blood
  • Aging/physiology
  • Animals
  • Blood Glucose/metabolism
  • Body Weight/genetics
  • Caves
  • Ecosystem*
  • Feeding Behavior*
  • Female
  • Fishes/blood
  • Fishes/physiology*
  • Glycation End Products, Advanced/blood
  • Homeostasis
  • Insulin/metabolism
  • Insulin Resistance*
  • Male
  • Mutation
  • Receptor, Insulin/genetics
  • Receptor, Insulin/metabolism
  • Starvation*
PubMed: 29562229 Full text @ Nature
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.