UMD Researchers Receive $1.6 Million from NIH to Study the Effects of Altered Insulin Signaling in Development

Dr. Stahl and Dr. Telugu at the Campus Farm

Image Credit: Melissa Rogers, College of Agriculture & Natural Resources, UMD

November 13, 2018 Samantha Watters

You’ve heard: you are what you eat; but have you heard: You are what your grandmother ate? UMD researchers are exploring this phenomena by more closely examining the genetic and hereditary components behind insulin signaling, connected to poor nutrition during pregnancy and low birth weight, and contributing to the development of diabetes and other major diseases related to metabolism.

Chad Stahl, Chair of Animal & Avian Sciences, and Bhanu Telugu, Associate Professor in the same department, are principal investigators on a new $1.6 million grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), an institute of the National Institutes of Health (NIH). This grant is funded out of the “dual purpose with dual benefit” grant program, specifically for research addressing both animal and human health, and coming out of a large need for more studies in model organisms that are agriculturally relevant.

Nutrition status of the mother during pregnancy has a profound effect on the growth and metabolism of the child, and not just while that child is in the womb. Poor nutrition during pregnancy and other risk factors that interfere with nutrient availability predispose the offspring to stunted growth and metabolic diseases later in life. Nutrition of mothers doesn’t just affect immediate offspring, but can carry across generations, the researchers say. The health of mitochondria—organelles within cells that convert chemical energy from food to usable energy—can be harmed by poor nutrition, and when passed down through generations, can effectively program the body to expect poor nutrition throughout life. This leads to smaller organs and an inability to process necessary nutrients, contributing to metabolic diseases.

This is true in animals and humans, with low birth weight being a major risk factor for obesity, heart disease, and diabetes in humans. “This occurs naturally in pigs, with low birth weight piglets eating the same amount of feed as their littermates, but growing slower and having lower market weight, causing economic losses to the farmers,” says Telugu.

Pigs also happen to be a particularly valuable model organism for the study of diabetes, heart disease, and obesity. “Pigs are the best animal model for neonatal nutrition - the metabolism and physiology of pigs and humans are extremely similar,” says Stahl. His expertise is in metabolic function and how this relates to nutrition and insulin resistance.

Telugu is proficient in working with CRISPR/Cas, a tool used for gene editing. In this case, Telugu is looking at a specific gene (GRB10) that has been shown to inhibit insulin signaling and lead to insulin resistance. This gene is linked to low birth weight and diseases like Silver-Russell syndrome, as well as obesity, diabetes, and cardiovascular or metabolic diseases.

“There is evidence that knocking out the gene leads to larger, healthier offspring with better insulin sensitivity who are less likely to develop diabetes and other metabolic diseases,” says Telugu. “But we don’t know exactly how this mechanism works, or how this is passed down through generations. With the availability of genome editing tools to over or under-express a gene, we can dissect specific pathways and monitor the effects across multiple generations.”

This work can be used to genetically select for animals that are more viable and have less risk of low weight and meat yield, while also applying specifically to prevent metabolic diseases and develop new treatments in humans. “If we can prove that this gene is instrumental in the development of metabolic diseases and diabetes, we can provide an additional screening tool to produce novel drugs that work on this signalling pathway, or even to prevent diabetes from occuring,” says Stahl.