It seems there is no limit to hummingbird superpowers. Blessed with the manoeuvrability of insects and high-speed vision, the nimble birds fuel their whirlwind lifestyle with a diet of sugar-charged nectar. Yet, by night, the animals wind down their metabolism, resorting instead to burning fat. Knowing that the birds must switch their metabolism back in the blink of an eye after their first morning sip of nectar, Ken Welch and Raafay Sayed Ali from the University of Toronto Scarborough, Canada, wondered how the frenetic creatures manage the feat. They explain that mammals depend on a pool of sugar-transporting proteins, known as GLUTs, to maintain the delicate balance between the sugar in their blood and cells. However, hummingbirds lack one essential transporter, GLUT4, which is key for humans and other mammals to regulate their bodies’ sugar use. Intrigued by the birds’ unconventional sugar-charged way of life, Ali, Morag Dick and Welch decided to monitor which GLUTs the birds depend on and where they are produced in the body to learn more about how they manage their sugar levels.
Collecting 12 wild ruby-throated hummingbirds (Archilochus colubris), Ali fed half of the birds with a limitless supply of sugar syrup, while the remaining six birds took an hour's rest with no syrup on tap. Then, he collected samples of the birds’ blood, to measure their sugar levels, in addition to portions of the birds’ muscles, heart and liver, to find out which GLUTs were key to keeping the tissues fuelled and how that changed when no nectar was available.
But then the team ran into technical issues. Explaining that scientists use specialised antibodies to reveal whether a tissue contains certain proteins, Welch recalls how the antibodies that were designed to recognise human GLUTs, which can be picked off the shelf, failed to recognise the hummingbird GLUTs. Instead, Ali, with help from William Wong and Dylan Sarver at Johns Hopkins School of Medicine, USA, designed customised antibodies, to track the sugar transporters produced by the hummingbirds.
Equipped with the new antibodies, the team, with analytical support from Lily Hou (University of Toronto Scarborough), discovered that the unfed birds quickly reduced the amount of GLUT1 and GLUT3 in their flight muscle and GLUT3 in the liver. ‘Raafay spent long hours in the lab, wrestling with the protocol details to generate these important results’, says Welch. And when Saad Muhammad (University of Toronto Scarborough) checked the amount of glucose circulating in the blood of the fed and unfed birds, it was apparent that the unfed birds were rapidly removing GLUT1 and GLUT3 from their bodies to ensure that their impressively high blood sugar levels (∼30 mmol sugar l−1) did not fall – normal human blood glucose levels are around 5 mmol l−1. ‘We had imagined that blood glucose levels would fall rapidly once fasting began’, says Welch, who was surprised that the hummingbird's GLUT1 and GLUT3 proteins appear to have stepped in to replace some human GLUT4 roles.
In addition, Muhammad checked the well-fed birds’ fructose blood levels, which were astronomically high (5 mmol l−1) compared with humans’ (∼0.3 mmol l−1), although an hour after the birds’ sugary syrup was taken away, their fructose levels had plummeted to almost zero. And, when Ali checked the fructose-transporting GLUT2 and GLUT5 proteins, they were similar to those of the fed birds, explaining how the bird's blood fructose levels were depleted as the proteins shuttled sugar into the tissues to keep them fuelled.
Sugar-junkie hummingbirds have overcome the challenges of regulating their blood sugar levels without the benefit of GLUT4 and Welch is keen to understand precisely how the animal's unique transporters help hummingbirds maintain a healthy blood sugar balance.