Type 2 diabetes is a metabolic disorder in which the body’s cells don’t adequately use insulin from the pancreas to turn glucose into energy. The result is high blood sugar levels. The primary causes of type 2 diabetes are genetic and lifestyle factors, such as a lack of exercise and obesity. With the global rise in obesity, the number of people with the disease has grown profoundly over the past 20 years. In 1980, 5.5 million people in the United States were estimated to have the disease compared with 30.3 million in 2015. And in 2017 the CDC released a report* showing “more than 100 million U.S. adults are now living with diabetes or prediabetes.”
Scientists work with animal models to better understand type 2 diabetes to treat the disease. They have developed specialized animal models that mimic the condition. One line of mice, known as KK mice, develop obesity and glucose intolerance that lead to type 2 diabetes. Another rodent model, the Zucker diabetic fatty rat, is bred to be a precise model of human type 2 diabetes.
KK mice (Courtesy Jackson Laboratory) Zucker fatty diabetic rat (Courtesy Joanna Servaes)
Working with Zucker rats, researchers have opened a new front in the war on diabetes: hormone therapy. Using a peptide called TLQP-21, researchers at Duke University were able to demonstrate improved insulin production and blood sugar levels amongst the treated Zucker rats. Follow-up studies suggest the effect may be similar in human cells and the drug could have fewer side effects than other treatments in use today.
Animal research into type 2 diabetes is not new. In fact, it has been going on for nearly 100 years and was the basis for the development of the most-prescribed diabetes drug in the world, Metformin. In the 1920s, K. Slotta and R. Tschesche published a paper claiming that metformin lowered blood sugar in rabbits. The results were largely overlooked, especially with the advent of insulin. In 1957, French researcher Jean Sterne renewed study of the drug, introducing the first human trials, which were largely successful. Metformin gained approval in the United States in 1994 after undergoing FDA studies in mice, rats, and rabbits.
A team of scientists at the Mayo Clinic has been working with mice to develop a new therapy that may protect patients from developing type 2 diabetes. As people age, their bodies accumulate a type of cell that is no longer able to divide – senescent cells. These cells release molecules that may cause type 2 diabetes by harming important cells in the pancreas. Darren Baker and Jan van Deursen, molecular biologists at the Mayo Clinic in Rochester, Minnesota, genetically engineered mice so that their senescent cells would die off when the mice were injected with an experimental drug. The mice whose senescent cells were eliminated were generally healthier than non-treated mice and lived an average of 20-30% longer. Researchers say this therapy might have a large impact on the progression of type 2 diabetes and related complications.
Type 2 diabetes research highlights the importance of studying a diverse array of animal models. The peptide that led to the development of the insulin alternative drug Lyxumia was isolated from the salivary gland of the Gila monster (Heloderma suspectum). Our friends at Speaking of Research tell it best in their blog post on the topic.
Reticulated Gila monster (courtesy Wikipedia)
With type 2 diabetes affecting so many people worldwide, animal testing and research is set to become even more essential to the development of new and more effective treatments. The CDC estimates that more than 1 out of 3 Americans has prediabetes – over 86 million people. More effective medicines will not only improve the lives of those living with diabetes, but also help cut healthcare costs. Medical costs for people with diabetes are twice that of nondiabetics. The 2012 cost of diabetes to the nation was an astounding $245 billion – $176 billion in medical costs and $69 billion in lost productivity. Improving lives and reducing healthcare costs is good not only for people living with the disease but also for the nation.
*Updated May 2018