Subterranean Fishes of the World

3256

2017

AIM 2017

We see tremendous variation in metabolism among different populations; however, how these traits evolved remain poorly understood. Mutations in glucose regulation can lead to severe pathologies, yet we still see variation in glucose regulation in nature. The cavefish Astyanax mexicanus provides us a unique opportunity to investigate how metabolic traits like glucose regulation can evolve among different populations. Here we show that cave-adapted populations of the A. mexicanus have insulin resistance in the skeletal muscles. As a consequence, the cavefish exhibit drastically altered blood glucose profiles which coincidentally lead to increased body weight. We identified a coding mutation in the insulin receptor of the Tinaja and Pachon cave populations. The mutation is linked to increased body weight in surface/Tinaja F2 hybrids carrying the mutation. Humans carrying the same mutations have Rabson-Mendenhall syndrome (a severe form of insulin resistance). We point out that we were unable to detect negative health effects in the cavefish commonly associated with diabetes. Not only do the cavefish tolerate dramatic acute changes in blood glucose levels better than the surface fish, but also do not accumulate advanced glycated end-products (AGE)’s associated with chronic hyperglycemia and the progression of diabetes-associated pathologies. We hypothesize that the cavefish have a acquired compensatory mechanisms that allow them to avoid the pathologies with aberrant glucose regulation. This study provides novel insight to the larger question of metabolic evolution and may lead to understanding relevant to human metabolic disease.

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