Diabetes: a complex disease with pancreatic cells in the spotlight

Experts discuss the importance of the ADI islet core to the global diabetes research and the importance of understanding pancreatic cell dysfunction in diabetes development.

Stepheny Zani - 14 June 2021

In the last webinar from the series organized by the Alberta Diabetes Institute (ADI) to celebrate the 100th anniversary of insulin discovery, ADI members and experts in pancreatic islet cells Patrick MacDonald and Jean Buteau talked about the central role of the pancreas in diabetes. MacDonald highlighted the contribution of the ADI IsletCore, a centre that receives pancreas donations and distributes isolated pancreatic islets to other scientists, to diabetes research worldwide. Buteau provided an overview of Type 1 and 2 diabetes (T1D and T2D), focusing on the role of beta cells.

Here are important messages from this webinar.

From the ADI islet core to the world

The successful approach used by scientists at the ADI IsletCore to isolate islets from donated pancreas has resulted in a global supply of pancreatic tissues and contributions in many diabetes-related studies. These studies cover many facets of diabetes research, including the investigation of the impact of environmental pollution on islet function, the modulation of islet function and gene expression to understand diabetes risk, strategies to improve transplants to treat diabetes and the identification of metabolic signalling pathways that regulate insulin secretion. More recently, the IsletCore has contributed to a study showing that SARS-CoV-2 is able to infect pancreatic beta cells.

New approach taken to understand problems in pancreatic hormone secretion

Insulin and glucagon are hormones that are vital for maintaining normal ranges of blood sugar. They are produced by beta and alpha islet cells, respectively, and their secretion is impaired in T2D. Researchers are now connecting the changes at the molecular level of islet cells to their function. Islet cells release hormones after an electrical signal and by linking the electrical pattern exhibited by islet cells with their gene expression, researchers can identify pathways that control the cell’s function and insulin or glucagon secretion. By using this technique, researchers have learned that both beta cells and alpha cells are dysfunctional in T2D, and that alpha cells exhibit variable maturation stages and glucagon secretion.

T2D development from a beta cell point of view

Pancreatic beta cells have a critical role in diabetes development and their mass is important to preventing the onset of T2D. Upon exposure to several environmental and genetic factors, individuals may develop obesity and eventually insulin resistance. Insulin resistance induces an increase in insulin secretion and beta cell mass to maintain blood glucose regulation. Although some insulin-resistant individuals will not develop T2D, around 20 per cent of them will progress to having beta cell failure and a decrease in beta cell mass, which causes a decrease in insulin secretion and hyperglycemia. Many factors are involved in beta cell dysfunction and death, such as the toxic effects of high blood sugar and lipids, oxidative stress, inflammatory processes and epigenetics.

T1D as a beta cell disease and not simply an autoimmune disease

T1D is an autoimmune disease culminating with beta cell destruction by the immune system and insufficient insulin production. Studies show that gene expression changes may happen before the autoimmune attack to beta cells. This theory proposes that T1D is a beta cell disease before it becomes an autoimmune disease. Proponents believe that many types of stresses, in particular endoplasmic reticulum stress, lead to beta cell death and cause changes in protein expression, eventually activating the immune system.    

The beta cell point of view in T1D and T2D provides an opportunity for the development of pharmacological and nutritional therapeutic measures to improve the beta cell environment and potentially prevent or delay the onset of both types of diabetes.

To complete the celebration of the 100th anniversary of the discovery of insulin, ADI will be presenting a half-day symposium on June 16, from 8:30 a.m.-1 p.m.