Type 2, or adult-onset diabetes, affects human populations worldwide. Data collected 40 years ago by the Navy Marine Mammal Program (MMP) at SSC Pacific may open the door to novel approaches in controlling and potentially curing this disease in humans.
People with type 2 diabetes are insulin resistant; their bodies produce insulin but do not use it properly. Because their bodies cannot effectively store glucose, high sugar levels build up in the bloodstream, which can lead to kidney, neurological or cardiovascular damage, or even death.
Dr. Stephanie Venn-Watson, director of clinical research for the National Marine Mammal Foundation (NMMF), recently identified the bottlenose dolphin (Tursiops truncatus) as an important natural animal model that complements type 2 diabetes in humans.
"This discovery may lead to applicable medicine that will benefit the health of both dolphins and humans," said Dr. Venn-Watson, who worked as the MMP's epidemiologist for seven years but recently transitioned to NMMF.
Dr. Venn-Watson's research began in 2007, using over 1,000 blood samples collected over seven years, as part of an effort to determine normal reference ranges for dolphins fasted overnight. While retrospectively comparing blood samples from recently fed MMP dolphins with dolphins that had not eaten overnight, an interesting and unexpected discovery was made. The blood samples from the fasted dolphins looked similar to samples collected from people with type 2 diabetes. However, once those same dolphins were fed, they changed back to a non-diabetic state.
"We concluded that dolphins have a diabetes-like metabolism that appears to switch on with fasting and off with feeding. Interestingly, an abnormality has been reported in a fasting gene found in people with type 2 diabetes that causes the switch to remain on. If humans could have control over diabetes with a fasting switch, similar to dolphins, this may advance efforts to cure diabetes," said Venn-Watson.
This finding led to follow-on research efforts and the discovery of MMP data from dolphin feeding studies conducted in the 1970s. Hourly blood and urine values were collected for 24 hours from a set of dolphins fed either sugar or protein.
"Dolphins fed sugar had hyperglycemia lasting at least 10 hours, similar to people with diabetes, but had good glucose control with a high-protein, low-sugar meal," said Venn-Watson. A steady supply of blood glucose is required by the large brains of primates, including humans, and cetaceans, including dolphins. As a means to transport the needed amounts of sugar to the brain, adult red blood cells found in only these two species among all animal groups have evolved to become extremely permeable to glucose.
"These physiological similarities between dolphins and humans may help explain why both have the potential for type 2 diabetes, a glucose-driven disease," said Venn-Watson.
Primates and cetaceans may share similarities in their development of insulin resistance. Prior to the last ice age, carbohydrate-rich primate diets provided a steady supply of blood glucose to the brain. Upon switching to a high-protein, low-sugar diet forced by lack of plant material, primates may have developed insulin resistance as a mechanism to conserve blood sugar.
Similarly, when cetaceans transitioned from land to ocean animals 55 million years ago, they also likely switched from a high-carbohydrate to a high-protein, low-sugar fish diet and, just like humans, may have developed insulin resistance to keep sugar in their blood.
Unlike humans, however, dolphins continue to eat fish and use insulin resistance to their advantage, while people have reverted back to a high-carbohydrate diet. Dietary sugar, combined with an insulin gene that remains on, leads to a surplus of blood sugar and creates diabetes.
"Understanding how and why insulin resistance has evolved in dolphins, and discovering how dolphins control their fasting switch will not only directly benefit dolphin health, but may provide clues to treating diabetes in humans," Venn-Watson said. "We're actively seeking collaboration with the diabetes research community to further this work.