Research from the UBC Laboratory of Molecular Signalling in Diabetes suggests insulin pathways could be more diverse than previously thought. The results have the potential to inform personalized nutrition care for the management of diabetes.
The findings of the ongoing study were published in Cell Metabolism in July. They showed variation in individuals’ insulin responses to the three macronutrients: carbohydrates, fats and protein. The study found fats could stimulate insulin release for some people, challenging the current consensus that fats have a negligible effect on insulin levels, unlike carbohydrates or some proteins.
Insulin, the hormone responsible for moving sugar from the bloodstream into cells for energy, is secreted by clusters of cells in the pancreas called islets. Consuming carbohydrates alters blood sugar levels, generally prompting a spike in blood sugar followed by an insulin response.
“When most labs study islet function — how much insulin these islets release — they just look at glucose,” said Dr. Jelena Kolic, the study’s lead author and research associate at the lab.
Researchers collected islets from deceased donors and each sample was exposed to a different macronutrient one at a time.
The majority of islets secreted the most insulin in response to carbohydrates. Nine per cent responded more strongly to protein than either carbohydrates or fats. However, eight per cent responded most strongly to fats, opposing the idea that fats have little to no effect on insulin secretion.
“We were really shocked with the fatty acid responses,” Kolic said.
The first time one of the study's co-authors saw a high insulin response to fats, the research team rechecked the solution to make sure it hadn’t been confused with a high-glucose solu tion. It took several more instances for the team to recognize the discovery they had made.
A key factor behind this breakthrough was the study’s scale.
“This was, to our knowledge, one of the biggest studies done when it comes to looking at human islets,” Kolic said.
The study, which began in 2016, examined islets from 140 donors. With fewer samples, the islets that responded most strongly to fats might have been missed completely or dismissed as an outlier.
Islets from donors with Type 2 diabetes — a disease characterized by insensitivity to insulin — unsurprisingly displayed a delayed insulin response to carbohydrates. However, insulin responses to protein were unimpaired, potentially supporting the idea of individualized diabetes management.
For example, if a certain type of protein could stimulate a diabetic person to produce enough insulin, their diabetes could possibly be controlled by increasing the levels of the protein in their diet.
The researchers used multi-omics to better understand the mechanisms underlying these responses. This involved collecting several data sets from the islet tissues, such as their proteins and RNA transcripts, the molecules responsible for creating proteins from DNA. They analyzed the relationship between these datasets and the islets’ insulin responses.
Researchers also found correlations between the abundance of some proteins and insulin responses. But they also found hundreds of novel, unexplored proteins.
In the future, Kolic hopes to further study these proteins and how they affect insulin release. They are expanding the study to investigate glucagon, another hormone secreted by islet cells which has the opposite actions as insulin.
“Science is hard,” said Kolic. “If you're really interested in an answer, there's a way to figure out what the answer is. It just might not always be a direct line.”
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