This year’s ADA Pathway to Stop Diabetes Symposium features six recent award recipients, who will discuss their research supported by the Pathway to Stop Diabetes® initiative. The two-hour session begins at 1:45 p.m. Saturday in room 31.
Joshua P. Thaler, MD, PhD, Associate Professor at the University of Washington Diabetes Institute, will present his research into inflammatory signaling in high-fat diet (HFD)-induced hyperphagia and obesity. He will discuss astrocytes and microglia, the two major glial classes. These parts of the gliosis response modulate inflammatory signaling and increase the energy homeostasis set point.
Dr. Thaler received his Pathway award after discovering HFD-fed animals and obese humans developed gliosis in the hypothalamus similar to, although in a milder form than what occurs in brain diseases such as Alzheimer’s or multiple sclerosis.
A study from Dr. Thaler’s group, “Astrocyte IKKβ/NF-κB Signaling Is Required for Diet-induced Obesity and Hypothalamic Inflammation,” was published in the April 2017 issue of Molecular Metabolism. In the study, HFD-fed mice with a tamoxifen-inducible astrocyte-specific knockout of IKKβ showed that preventing inflammatory signaling in astrocytes led to thinner animals.
A concurrent study, co-authored by the lab of Suneil Koliwad, MD, PhD, Assistant Professor of Medicine at the University of California, San Francisco, and recently accepted for publication at Cell Metabolism, found that inflammatory signaling in microglia is also important in the development of obesity in mice.
In both cases, HFD consumption drives the inflammatory process and activation of astrocytes and microglia. An early glial response to the diet occurs before mice start to gain weight and is part of the pathologic process leading to obesity.
“The deeper implication that we don’t have proof for—but are working toward—is the idea that there’s a structural change that takes place that resets our set points,” Dr. Thaler said. “Otherwise, why can’t we just lose the weight that we gain?”
Kathleen A. Page, MD, Assistant Professor of Medicine in the Department of Internal Medicine, Division of Endocrinology, at the University of Southern California Keck School of Medicine, will discuss the Brain Child Study, which examined the effects of fetal exposure to maternal gestational diabetes (GDM) on childhood adiposity, independent of maternal pre-pregnancy obesity status.
“The number of women affected by gestational diabetes during pregnancy is increasing, and this may be one factor contributing to the increased prevalence of childhood obesity and type 2 diabetes,” Dr. Page said. “Our study suggests that in utero exposure to maternal GDM may specifically increase children’s stores of abdominal fat, which is associated with an increased risk for metabolic diseases, including type 2 diabetes and cardiovascular disease.”
While child weight, body mass index (BMI), and total body fat were not significantly associated with maternal GDM and pre-pregnancy BMI in the study, child waist-to-hip ratio was significantly greater for GDM-exposed children and positively associated with maternal pre-pregnancy BMI. Those associations were independent of each other, Dr. Page said.
Praveen Sethupathy, PhD, Associate Professor and a Principal Investigator in the Department of Biomedical Sciences at Cornell University, will discuss what he calls an important but understudied area: The molecular underpinnings of the effect of gut microbes and a high-fat diet on the intestine.
Dr. Sethupathy received his Pathway award to investigate how a class of microRNAs affect the intestine’s ability to renew itself, which in turn may affect its capacity to absorb nutrients or secrete hormones that help maintain energy balance in the body. He will discuss his latest findings and the importance of conducting these studies in the context of diverse genetic backgrounds.
“It’s now evident that the intestine is extremely important in the control of energy balance and in diabetes etiology,” Dr. Sethupathy said. “We need to dig deeper to define the genetic factors and molecular networks that maintain intestinal homeostasis, particularly in the face of a broad range of stimuli, including nutrients and microbes.”
Phillip J. White, PhD, Senior Research Associate at Duke Molecular Physiology Institute, will review unpublished findings that show a novel therapeutic avenue to treat and prevent type 2 diabetes.
Branched-chain amino acids (BCAAs), which come from certain proteins in the diet, are linked to the development of type 2 diabetes. But how circulating BCAAs are connected to abnormal glucose and lipid metabolism remains unclear. Using Zucker-fatty rats, Dr. White and his colleagues discovered that some components of the molecular network that regulate BCAA catabolism also interact with enzymes involved in glucose and lipid production.
“We’ve uncovered a mechanism by which glucose and lipid metabolism is integrated with BCAA metabolism in the liver,” Dr. White said. “This regulatory node represents a novel therapeutic target for the treatment of insulin resistance and non-alcoholic fatty liver disease.”
Zhen Gu, PhD, Professor in the Joint Department of Biomedical Engineering at the University of North Carolina and North Carolina State University, will discuss his research involving “smart insulin.” He will review his team’s studies into the use of smart insulin patches and red blood cells to regulate glucose levels.
“Glucose-responsive insulin delivery is an important research topic that could profoundly change the life of people with diabetes,” Dr. Gu said. “Many research and industrial labs are currently working in this field.”
Daniel J. Ceradini, MD, Director of Composite Tissue Allotransplantation and Director of IRPS Laboratories at New York University Langone Medical Center, will discuss his research efforts to target a cellular pathway that underlies diabetic complications.
“We have identified a critical molecular pathway that is disrupted by diabetes and hyperglycemia,” he said. “By using design-driven methodology, we have successfully developed a novel therapeutic and delivery system that restores tissue regeneration in diabetes.”