On Feb. 22, the Research Institute of the McGill University Health Centre (RI-MUHC) presented a lecture from members of the RI-MUHC community, as part of their ongoing Distinguished Professors Lecture Series. This month’s distinguished professor was Guy Rutter, a professor of Medicine at the University of Montreal and researcher specializing in type 2 diabetes, a disease that affects more than 10 per cent of the global adult population.

For people with diabetes, their body is unable to properly metabolize glucose, a type of sugar. 

After eating or drinking carbohydrates—a nutrient found in sugary or starchy foods—beta cells in the pancreas sense an increase of glucose in the bloodstream. In response, they release a hormone called insulin. Insulin allows cells to uptake and breakdown glucose, thereby lowering blood sugar levels. 

“It’s either the destruction or the failure of [beta] cells to respond appropriately to an elevation of blood glucose which underlies all forms of diabetes mellitus,” Rutter explained in the lecture. 

The impacts of unmanaged diabetes are serious. An insufficient insulin response underlies chronic high blood glucose, which can damage small blood vessels, causing nerve damage and kidney disease.   

In type 1 diabetes, beta cells are destroyed in an auto-immune reaction that typically begins in childhood. In type 2 diabetes, however, beta cell mass is not strongly reduced. Instead, a complex interaction between environmental factors and genetic predispositions to the disease hinder insulin release. 

Rutter’s research centres on the islets of Langerhans, clusters of cells found in the pancreas that release metabolic hormones—including insulin—into the bloodstream. Beta cells are one variety of cell found in these islets.

Recent research shows that beta cells function as fuel sensors, continually monitoring and responding to their own energy levels. The more glucose present in the blood, the more fuel in the form of ATP molecules will be produced in the beta cell. 

“[A high ATP level] is essentially used as a signal,” Rutter said. This signal opens voltage-sensitive calcium channels, flooding calcium into the beta cell. This influx of calcium is what triggers the release of insulin. 

Rutter and his team identified deficiencies in various steps of this process.

“The transporter [protein], which will allow glucose into the [beta] cell is more weakly expressed,” Rutter said. In addition, certain proteins which are absent in the mature beta cell remain present, disrupting normal cellular processes. 

“So you have a cell which is becoming much less specialized for ATP synthesis and detection and becoming much more run-of-the-mill,” Rutter added. 

Rutter also investigated newly described differences in the way beta cells communicate with each other. 

“Why do we have pancreatic islets? Why are they always about the same size—about 1000 cells give or take? And that’s the same whether you’re a mouse or a horse or a blue whale,” Rutter wondered. “There’s something special about the size, and there’s something special, perhaps, around the interactions between cells.” 

Rutter and his colleagues have identified leader, hub, and follower beta cells. When an islet encounters glucose, a wave of insulin is released. Leader cells start this wave, hub cells propagate it, and follower cells follow suit. 

By precisely destroying leader cells, Rutter stopped islets from producing insulin responses, even if a majority of beta cells were left undisturbed. 

Islet connectivity is also diminished in type 2 diabetes: Diabetic mice showed a loss of coordinated islet dynamics which was largely restored after they underwent vertical sleeve gastrectomy, a weight loss procedure. 

“[In type 2 diabetes], you don’t lose many beta cells—no more than 25 per cent. [But] if you’re losing a particularly important 25 per cent, that may have consequences for the overall secretion of insulin,” Rutter said. 

Currently, treatment of type 2 diabetes involves lifestyle changes along with medications and continual blood glucose monitoring.

“But none of these [medications] address the progressive loss of the function of the entire cell,” Rutter said. “If we can understand [genetic] variants […] we may have alternative new ways to personalize new drugs.”