Some bats survive and thrive with blood sugar levels that would be lethal to other mammals

Humans need to regulate their blood sugar levels to stay healthy and fuel their cells. Having too much or too little blood sugar can lead to serious health complications, and high blood sugar is a hallmark of the metabolic disease diabetes. New research from the Stowers Institute for Medical Research may provide potential solutions to metabolic diseases by looking to evolution and bats.

Published in Ecology of nature and evolutionThe study led by co-first authors, postdoctoral research associate Jasmin Camacho, Ph.D., and former Stowers researcher Andrea Bernal-Rivera in the lab of Stowers associate investigator Nicolas Rohner, Ph.D., reports the highest naturally occurring blood sugar concentrations ever observed in mammals, a finding that suggests bats have evolved strategies to survive, and even thrive, with this extreme trait.

“Our study reveals levels of blood sugar never seen in nature, levels that would be lethal and cause coma in mammals, but not in bats,” Camacho said. “We are observing a new trait that we did not know existed.”

Thirty million years ago, the Neotropical Hog-nosed Bat survived solely on insects. Since then, these bats have diversified into many different species by changing their diets. Starting with insects, different lineages now specialize in diets that include fruit, nectar, meat, and everything in between, even just blood.

“By studying animals that have been around for millions of years, we can begin to catalog the changes that have occurred during evolution,” Camacho said. “What makes Neotropical leaf-nosed bats so unique to study is that this group is made up of many different species with very diverse diets, which makes it possible to find answers about how diets evolve. We hope to extend this understanding to other mammals, including humans, where there may be ways we can learn to better protect our own health.”

To learn how bats diversify their diets, the team traveled to the jungles of Central America, South America and the Caribbean to conduct fieldwork over several years. These capture-and-release expeditions focused on performing glucose tolerance tests (a measure of blood sugar concentration) on nearly 200 wild-caught bats from 29 species after a single feeding of one of three types of sugars associated with insect, fruit or nectar diets.

“We saw different ways in which sugar is assimilated (absorbed, stored and used in the body) and how this process has become specialized due to different diets,” Bernal-Rivera said.

The mechanism for keeping blood sugar levels within a narrow, healthy range is called glucose homeostasis, which is typically regulated by the hormone insulin and is the root of the dysfunction in diabetes. Different species of leaf-nosed bats have a spectrum of adaptations to glucose homeostasis, ranging from changes in gut anatomy to genetic alterations in the proteins that transport sugar from the blood to cells.

“Frugivorous bats have perfected their insulin signaling pathway to lower blood sugar,” Camacho said. “At the other extreme, nectarivorous bats can tolerate high blood glucose levels, similar to those seen in people with unregulated diabetes. They have evolved a different mechanism, which does not appear to depend on insulin.”

Although the precise way in which nectar-eating bats handle glucose is still under investigation, the researchers found potential clues to alternative metabolic strategies for regulating glucose. Bats on a high-sugar diet were observed to have longer portions of their intestines and their intestinal cells had a larger surface area to absorb nutrients from food, compared to bats on other diets. Additionally, nectar-eating bats, distinct from fruit bats, have continuous expression of a gene responsible for sugar transport, a trait also observed in a species of hummingbird.

“This study is an extremely important resource for the field,” said Nadav Ahituv, Ph.D., professor of bioengineering and genetics at the University of California, San Francisco. “It provides not only metabolic characteristics of different bat species with different diets, but also their gut morphology, as well as candidate genomic regions and protein structural differences that could underlie dietary adaptations.”

“The datasets will fuel future research that aims to differentiate dietary differences among mammals and could advance the development of novel therapies for a variety of metabolic diseases in humans,” Ahituv said.