The circadian clock is a key biological pathway that interacts with and modulates metabolic pathways and other physiological processes. Many human tissues, including pancreatic beta cells and adipocytes, function in rhythmic cycles that are regulated by internal circadian oscillators.

In the symposium, Timing Is Everything—Circadian Rhythms in Health and Disease, on Friday, June 20, from 3:45–5:15 p.m. in Room W194 AB of the McCormick Place Convention Center, experts will discuss the role of the circadian clock in modulation of beta cell function and glucose homeostasis, and spotlight the benefits of time-restricted eating, a temporal dietary intervention grounded in circadian biology.

“Our body has a timetable of doing things at the right time,” said Satchidananda Panda, PhD, Professor and the Rita and Richard Atkinson Chair of the Regulatory Biology Laboratory at the Salk Institute. “For example, the gut has a rhythm for digestion and nutrient assimilation; the pancreas has a better time to respond to glucose and produce adequate insulin; and muscle has its own time to absorb glucose and be able to exercise.”

These rhythmic processes and timetables encapsulate the concept of the circadian rhythm.

“Disrupting the circadian rhythm can impair the body’s ability to maintain glycemic control and provide energy to organ systems,” said Dr. Panda, who will discuss the benefits of time-restricted eating.

He will be joined by Christine Doucette, PhD, Associate Professor of Physiology at the University of Manitoba, Canada, speaking about circadian regulation of pancreatic beta cells, and Aleksey Matveyenko, PhD, the J. W. Kieckhefer Professor of Regenerative Medicine and Physiology at the Mayo Clinic, who will review circadian regulation of glucose homeostasis in health and disease.

“The circadian rhythm has a complicated and multifaceted effect on diabetes pathophysiology,” Dr. Matveyenko said. “Circadian pathways are very important for modulation of adipose, liver, and skeletal muscle biology. It is important for beta cells to secrete insulin in circadian fashion, to avoid inappropriate insulin increase at night, for instance. Most importantly, it is critical for beta cells to optimize insulin production, processing, and secretion to the active (day) phase of the circadian cycle to meet the increased metabolic demands.”

Research by Dr. Matveyenko and colleagues has shown that the ability of beta cells to respond to different stressors is modulated by circadian genes.

“In type 2 diabetes, beta cells are pushed to produce more insulin, which can induce stress,” he explained. “The ability of beta cells to respond to/manage insulin secretion demands and other stresses, including inflammation and oxidative stress, is impaired if the circadian pathways are disrupted.”

Diabetes etiology involves both genetic and environmental components. Dr. Matveyenko pointed out that genome-wide association studies identified many type 2 diabetes-associated genes, including some circadian rhythm genes. The most widely recognized example is a melatonin receptor variant, although its mechanistic role in diabetes pathophysiology is still under investigation.

“I think where the field is heading is to try and apply our understanding of circadian biology and its impact on beta cells to develop approaches—behavioral, lifestyle, and/or pharmacological interventions—to help patients with diabetes,” Dr. Matveyenko said. “Time-restricted eating is perhaps the best example of such an approach where circadian biology can be leveraged to improve metabolism and, especially, beta cell function.”

Time-restricted eating has been shown to decrease body weight, glucose intolerance, hypertension, and dyslipidemia in human studies, Dr. Panda noted.

“Animal model studies show that mistimed eating can increase obesity risk, and conversely, time-restricted food intake can prevent and even reverse obesity, insulin resistance, and many diabetes-associated complications,” he said.

While the National Diabetes Prevention Program, led by the Centers for Disease Control and Prevention (CDC) and one of the largest public health-funded lifestyle intervention programs, codified the idea that lifestyle modifications can help people manage prediabetes and type 2 diabetes, there is a paucity of such large-scale studies since then, Dr. Panda said, adding that professional organizations such as the American Diabetes Association® have a crucial role to play in supporting efforts to standardize study protocols around the timing of meals relative to the circadian rhythm.