Study examining the body’s regulation of insulin yields promising new results

May 17, 2016

(ATHENS, Ohio) Significant new findings about the body’s process for regulating the release of insulin could have major implications for the treatment of type 2 diabetes.

The findings, published in Endocrinology by authors from the Ohio University Heritage College of Osteopathic Medicine and the University of Virginia, challenge widely held beliefs that diabetes damages the normal processes of insulin-producing pancreatic cell clusters, called islets. The study shows that the diabetic condition causes these islets to become overly sensitive to glucose, thus disrupting the normal patterns of insulin release and making the islets attempt to release more insulin than actually needed.

“By tricking these islets into thinking they are seeing less glucose, we seem to be able to restore normal function in diabetic islets,” said Craig Nunemaker, Ph.D., an associate professor at the Heritage College and co-author on the study.

Although the loss of function may be reversible in certain conditions, the study also found that high-glucose exposure may make cells more susceptible to other stressors that can disrupt normal insulin production.

“This suggests that interventions or treatments to restore the body’s ability to release insulin normally should be administered early in the disease process,” said Nunemaker.

Under normal conditions, the body releases insulin in timed pulses connected to a person’s activities like eating or exercising. These systematic releases are used to regulate energy levels. When that regulatory function stops, it is thought to be an early sign of type 2 diabetes.

In this study, researchers examined how exposure to varying glucose levels affected the pulsing function or pulsatility of diabetic-prone islets. They found that the ability to release insulin was not lost in diabetic islets. In fact, reducing glucose levels the islets are exposed to can restore pulsatility.

“The present study demonstrates for the first time to our knowledge that the mechanisms involved with producing oscillations are intact in the diabetic condition,” said Nunemaker. “However, the normal range of glucose needed to trigger oscillatory activity has shifted substantially in diabetic cells.”

The researchers found that when diabetic cells become more sensitive to glucose, they also become more susceptible to other stressors that can disrupt the insulin-pulsing function. In the study, researchers exposed islets to pro-inflammatory cytokines, which play a key role in the body’s immune system. An increased level of these cytokines is also associated with a higher risk of diabetes. They found that in a high-glucose environment, the pulsatility of diabetes-prone islets is more prone to disruption when exposed to pro-inflammatory cytokines.

“This study is important because a great deal of effort is focused on trying to get a diabetic pancreas to release more insulin to treat type 2 diabetes. Our study shows that in the early stages of the disease process, these cells appear to be working very hard to produce too much insulin compared to normal cells. By reducing their sensitivity to sugar, we seem to be able to restore the normal pattern and possibly the normal amount of insulin secretion needed to sustain the body’s energy needs. When the pulsing system is working normally, the evidence suggests that the body may respond better to treatment and be less likely to become insulin resistant. Also, maintaining a cycle of insulin release that includes resting periods could allow cells to work harder and more efficiently during times when the demand to process insulin is elevated,” said Nunemaker.

The study, “ Islet hypersensitivity to glucose is associated with disrupted oscillations and increased impact of proinflammatory cytokines in islets from diabetes-prone male mice,” recently published in Endocrinology, is authored by Nunemaker, Kathryn L. Corbin, Christopher D. Waters, Brett K. Shaffer, M.D.,  and Gretchen M. Verrilli.   

This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Mouse Metabolic Phenotyping Centers (www.mmpc.org) under the MICROMouse Funding Program Grant DK076169 and by National Institutes of Health Grant R01 DK089182. Additional support was provided by the Arnold and Mabel Beckman Foundation.

The Ohio University Heritage College of Osteopathic Medicine is a leader in training dedicated primary care physicians who are prepared to address the most pervasive medical needs in the state and the nation. Approximately 50 percent of Heritage College alumni practice in primary care and nearly 60 percent practice in Ohio. CARE LEADS HERE.