Gestational Diabetes Adversely Affects Pancreatic Islet Structure and Function in the Male Rat Offsp

The pancreas contains important structures called the islets that produce important glucose-regulating hormones, including insulin. Diabetes happens when the islets fail to produce enough insulin to control blood sugar, resulting in high blood sugar levels. Mounting evidence, from DREAM researchers and others suggests that what we are exposed to in early life (i.e. during fetal life) can affect our metabolic health later in life. For example, exposure of an unborn child to diabetes during pregnancy (gestational diabetes) is strongly associated with significant risk of type 2 diabetes development for that child later in life. A connection between gestational diabetes and diabetes risk in the offspring makes sense since cells in the islets of the pancreas undergo major structural and functional changes while a baby is developing in utero.

The purpose of this study was to characterize how exposure to gestational diabetes impacts islet function and gene expression profiles. We also examined whether gestational diabetes exposure further affected the offspring pancreatic islets when the offspring were challenged with consuming unhealthy diets consisting of high fat content and refined sugars.

How did we test our hypothesis?

Since it is challenging to test these research questions in people, we used a rat model of gestational diabetes. To induce gestational diabetes, female rats were placed on a high fat and high sugar diet. Following mating, these female rats became diabetic during pregnancy. After being weaned from their mothers, offspring were randomly placed on either a healthy low fat diet or a high fat and sugar diet. When the rat offspring reached the young adult stage, we isolated their islet cells and tested their ability to secrete insulin. We also used a technique called “RNA-Seq” to measure how exposure to gestational diabetes impacted the gene expression profile of the islets in the offspring.

What did we find?

We found that insulin secretion was reduced in islets from offspring born to mothers with diabetes. Insulin secretion was even lower if the offspring consumed a poor diet. Interestingly, when we examined gene expression, we found that genes that promote inflammation were increased in the islets from offspring exposed to gestational diabetes. Inflammation is a normal response to infection, but in this case, inflammation could be an early event that damages pancreatic islets, although this needs to be further examined in follow-up studies.

Why is this important?

While associations have been made between diabetes during pregnancy and the development of type 2 diabetes in the offspring, our study directly demonstrates the negative impact of diabetes exposure during pregnancy on insulin secretion by pancreatic islets. We also present the first data showing that exposure to gestational diabetes impacts gene expression in the pancreatic islets of the offspring. Given that the incidence of gestational diabetes appears to be on the rise, public health measures focused on maternal health could yield health benefits for both mothers and future generations.

The full text of the paper published in the latest issue of Endocrinology can be found HERE