Prior to the advent of insulin therapy in the 1920s, women with diabetes rarely became pregnant. Rarer still were healthy, live births.
With significant advancements in the management of diabetes, that’s no longer the case. But the chronic disease can still be a roadblock for couples trying to conceive.
Dr. Jennifer Hill, an associate professor of physiology and pharmacology.
New research at The University of Toledo funded by a grant from the National Institutes of Health could pave the way for new treatments for infertility in those with diabetes.
“Insulin is a critical molecule for permitting fertility. Animal experiments have shown that without insulin acting on the brain, reproductive hormones cannot be released,” said Dr. Jennifer Hill, an associate professor of physiology and pharmacology. “We’ve known for a long time that diabetes can negatively impact fertility in both men and women, but we didn’t know where this disconnect was happening.”
Hill, a neuroscientist who studies the endocrine system and reproductive health, has been working for years to unravel that mystery.
Insulin, which is produced by the pancreas, helps to regulate a number of metabolic processes, but its key jobs are controlling blood sugar levels and helping cells convert glucose from the food we eat into energy.
In the context of reproduction, insulin is necessary for the brain to release a hormone called GnRH, which is the master hormone that drives reproduction.
When insulin is lacking, or not properly recognized in the brain, the hormonal cycle breaks down, leading to reduced sperm production in men and irregular ovulation in women, both of which can result in difficulty becoming pregnant.
In 2019, Hill’s research team published a paper in the journal PLOS Biology outlining their discovery that insulin signaling was happening in brain cells called astrocytes.
While that discovery represented a major turning point in the field — researchers had previously assumed the insulin acted on neurons — unanswered questions remain, particularly about when astrocytes start to sense insulin and permit normal reproductive function.
“Is it in some of the earliest stages of life — prenatal even — or is astrocyte insulin responsiveness required around puberty? Or is it having effects in the adult as well? Any of those are possible,” Hill said.
Answering those questions is a key focus of her current research, which was recently funded by a five-year, $2.7 million grant from the National Institutes of Health.
The work also will examine different areas of the brain to determine which astrocytes the insulin is acting on as well as the pathways necessary to sustain fertility.
Keeping diabetes well-managed with diet, exercise and medications like Metformin can improve fertility, Hill said, but the long-term goal of her research is identifying new targeted therapies.
“People who are affected by infertility realize what a huge loss it is for them. It’s isolating and they often feel very alone,” Hill said. “The dream would be to get a drug that is more specific to the brain, more specific to the areas that affect fertility. I would really love to be able to relieve that burden for people.”
