Metformin Reexamined—Pleiotropic Effects in Mother and Offspring in Humans and Animal Models
Sunday, June 23, at 8:00 a.m. ET
Room W315
Orange County Convention Center
Effects and Consequences of Metformin Action in the Fetal Liver from Nonhuman Primates and Sheep
Stephanie R. Wesolowski, PhD
Associate Professor,
University of Colorado
What is your presentation about?
This talk will highlight recent data demonstrating how in utero exposure to metformin may affect the developing fetal liver.
How do you hope your presentation will impact diabetes research or care?
The goal of this talk is to raise awareness regarding the potential beneficial or harmful effects that metformin may have in the fetus.
How did you become involved with this area of diabetes research or care?
My lab has a long-standing interest in understanding how adverse intrauterine exposures impact fetal metabolic physiology and developmental programming. Given our focus in the fetal liver and how other intrauterine exposures like growth restriction may induce hepatic insulin resistance in the fetus, we became interested in how metformin could be used to improve fetal hepatic insulin sensitivity. However, growing concerns have arisen from metformin’s use in pregnancies complicated with gestational diabetes, which prompted our current studies aimed to understand metformin’s effects in the fetal liver.
Effects of Metformin and Maternal Overnutrition on Fetal Pancreas and Islet Mitochondria in Nonhuman Primates
Maureen Gannon, PhD
Professor of Medicine,
Vanderbilt University Medical Center
What is your presentation about?
It is estimated that two-thirds of U.S. women in their child bearing years are overweight or obese. Using a non-human primate model of maternal Western style diet feeding during pregnancy and lactation, we previously reported altered Beta:Alpha-cell ratio in vivo and insulin hyper-secretion ex vivo in offspring at one and three years of age, even when the offspring are weaned onto a healthy control diet. In this presentation, I will describe our analyses to determine the cause of this offspring islet phenotype. We have examined expression of genes involved in insulin secretion and Beta-cell maturity, and analyzed islet metabolic flux and mitochondrial morphology. In recent years, metformin use in pregnancy has expanded to include prediabetes, type 2 diabetes, gestational diabetes, PCOS, and pre-eclampsia. Given that metformin is not metabolized by the maternal liver and can be transported across the placenta, it can thus accumulate in fetal tissues and amniotic fluid at similar concentrations. Metformin is known to slow metabolism and growth, thus examining its potential effects on the development and function of critical metabolic organs such as the pancreatic islets, is important. I will also describe our studies examining how developmental metformin exposure affects fetal islet development and function in the non-human primate model.
How do you hope your presentation will impact diabetes research or care?
Pregnancy is a time when women are motivated to make lifestyle changes to benefit the metabolic health of their offspring. By understanding how maternal diet choices and drug exposures may affect the future metabolic health of offspring, we can better counsel women who are considering getting pregnant or who already are pregnant and help them make better informed decisions that can translate into better health outcomes for their offspring.
How did you become involved with this area of diabetes research or care?
My PhD is in cell and developmental biology, so I have a long standing interest in the developmental origins of health and disease. There is much research to show that, in addition to genetics and inheritance, the in utero environment has a significant impact on the development and later function of important metabolic organs such as the pancreas. While mouse models are useful to dissect the contributions of certain genes to the formation and function of insulin-producing Beta-cells, the non-human primate is a model that is more closely related to humans in terms of islet architecture and function. I am fortunate to be part of a multi-year, integrative consortium using this model to study the effects of maternal diet and drug exposures on the development and function of multiple tissues. As a group, we can take a systems biology approach to understanding how the maternal metabolic environment impacts the health and susceptibility to metabolic disease in the next generation.