Move over mice, canines may be next in line to study diabetes

Published: May 31st, 2017

Category: Feature, News

STORY AT A GLANCE

  • Dogs develop a form of diabetes that has similarities to type 1 diabetes in humans
  • UF investigator and clinical assistant professor in veterinary medicine Allison O’Kell, DVM, is exploring the pathogenesis of canine diabetes to study possible similarities between how the diabetes develops in dogs and humans.
  • One possible outcome from this research is the ability to study dogs as an alternative animal model for type 1 diabetes, and improve our understanding of this disease in both humans and dogs.

Mouse models have been used to study diabetes for decades, but one University of Florida Health investigator is looking no further than man’s best friend for new insights into diabetes.

“Diabetes is a common endocrine disorder affecting less than 1 percent of dogs, and some breeds are more susceptible than others,” said O’Kell.

Before Allison O’Kell, DVM, MS, joined the University of Florida College of Veterinary Medicine as a clinical assistant professor, she saw canine patients among other small animals as a veterinary internal medicine specialist.

“I was trained mostly as a clinician with some research on the side, but lately that’s been flip-flopped, “said O’Kell. “Dogs might be considered a large animal to most basic science researchers, but to me it’s still a small animal that may be helpful for studying the development of type 1 diabetes.”

Dogs and Diabetes

Dogs develop two kinds of diabetes: insulin deficiency diabetes, which is considered to be similar to type 1 diabetes in humans, and insulin resistance diabetes. Both types of diabetes in dogs are treated with insulin, at least initially. Some dogs with insulin resistance diabetes have an underlying cause to the disease, and may go into remission for some time after treatment, but in general this is less common than insulin deficiency diabetes in canines in the United States. O’Kell and her team’s research focuses on insulin deficiency diabetes in canines.

Canines, or dogs, are not new to diabetes studies. Researchers have been looking at diabetes in dogs since the late 1800s, which led to some of the first discoveries of insulin, a hormone that allows glucose, or sugar, to be utilized by the  body’s cells for energy. Patients (dog or human) with diabetes cannot produce or utilize enough of their own insulin to manage blood glucose levels.

While those initial studies explored diabetes in dogs through experiments, O’Kell’s research focuses on the natural development of the disease in dogs. Susceptible breeds include Samoyeds, several types of terriers, and miniature Schnauzers, while Golden retrievers, Boxers and German Shepherds are some of the least likely to develop canine diabetes. O’Kell also points out that mixed breed dogs can develop diabetes, too.

O’Kell says that more research is needed within breeds to be able to continue to look for genes associated with the disease, and some genes may be similar to their human counterparts.

Some clinical manifestations of the disease are also similar. For example, many dogs are diagnosed with diabetes after clinical signs appear. These may be consistent with clinical signs in diabetic people, like increased water intake and increased urination in combination with high blood glucose levels.

“Normal blood glucose ranges in dogs are similar to people,” said O’Kell. “Since glucose doesn’t spill over into the urine and cause clinical signs until glucose levels are quite elevated, it is possible that we’re missing some early cases of diabetes in dogs because many animals aren’t having regular blood work to monitor blood glucose.

One opportunity for further research is exploring the beginning stages of the disease in dogs, which would require monitoring dogs from highly susceptible breeds. One outcome of this research could be gathering enough information to compare the development of diabetes in dogs to the pathology in humans.

“While juvenile onset of type 1 diabetes is common in humans, it is not common in dogs,” said O’Kell. “Most dogs show clinical symptoms around ages 5-7 years.[OL1]

Human vs. Canine Anatomy

Canine anatomy is very similar to human anatomy, with a few differences. While dogs and humans have different shaped pancreases, their functions are quite similar. For example, the canine pancreas has a right and left limb whereas the human pancreas has a head and a tail. However, the right side of the canine pancreas is analogous to the “head” of the human pancreas.

Canines also have islets, which are housed in the pancreas, comprising of multiple kinds of cells, including beta cells, which humans also have. Beta cell destruction is part of the pathogenesis of type 1 diabetes.

Dogs with diabetes experience a high degree of beta cell loss, similar to beta cell loss in humans with type 1 diabetes. A major difference between human and dog islets are the number of alpha cells. Dogs, on average, have fewer alpha cells in proportion to beta cells in their islets. Alpha cells produce glucagon, which is a hormone with opposite effects to insulin.

“Based on a recent study evaluating the pancreas in diabetic canines the authors proposed that the relative lack of alpha cells might help preserve insulin/ glucagon balance and protect from clinical signs of disease until extreme beta cell loss has already occurred,” said O’Kell. “From the results of that study, we have to wonder if we are missing opportunities to learn more from studying dogs in early onset of the disease.”

In addition, O’Kell’s team is exploring the role of autoimmunity in canine diabetes. Type 1 diabetes in humans is largely thought to be an autoimmune disease. While there is some evidence to support the presence of an autoimmune component in dogs, study results have been inconsistent and more research is needed to clarify the role of autoimmunity.

“Is there an untested or unidentified antigen present? Are we missing the window to detect autoimmunity?” asks O’Kell. “We may also be in a situation where some cases of canine diabetes are simply not caused by an autoimmune disease.”

Pancreatitis is also a very common issue in dogs. According to O’Kell, while pancreatitis may contribute to the development of diabetes in some dogs, there is too much variability in studies to know how commonly pancreatitis plays a role in the development of canine diabetes.

Next Steps

O’Kell and her research team are studying pet dogs that develop diabetes. All of the dogs live at home with their owners and thus share the same environments as people, which is a potential advantage over studying animals that live in a laboratory setting. The team has identified priority areas for research moving forward in this field, which include further investigation of pancreatic function in diabetic dogs over time, as well as novel methods to look for evidence of autoimmunity. Additionally, O’Kell hopes to find biomarkers that might allow prediction or earlier detection of diabetes in dogs The goal of the research is to better understand the disease in dogs, which may translate to better understanding of the disease in people. The idea that this research may help both man and man’s best friend is a driving force for O’Kell moving forward.

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