Journal News

Sorting and secreting insulin
by expiration date

The age of insulin parcels may matter, researchers say, when it comes to diagnosing and treating diabetes
Anand Rao
July 30, 2020

A study in the Journal of Biological Chemistry describes a new way to determine the age of insulin-storage parcels, known as granules, and sheds light on how their age affects their release into the bloodstream. The findings could help experts better understand diabetes and fine-tune therapies for it.

Insulin-Secretion-445x935.jpg
Credit: Belinda Yau
This series of live cell images represents insulin granule secretion. Syncollin-dsRedE5TIMER was used to visualize the age of secretory granules in beta cells subjected to low or high glucose conditions.

Insulin is a hormone that manages the level of sugar, or glucose, in the bloodstream. It is secreted by the pancreas into the bloodstream when blood sugar levels rise. When insulin circulates in the bloodstream, muscle and other cells absorb glucose to use it as fuel, and so blood sugar levels decline. In Type 2 diabetes, formerly known as adult-onset diabetes, this process fails. Glucose builds up in the blood, either because the pancreas cannot produce enough insulin to keep up with dietary sugar intake or because the gland simply isn’t working as it should.

About one in 10 Americans and more than 415 million people worldwide have diabetes, according to the Centers for Disease Control and Prevention. Up to 95% of them have Type 2. Treatment often requires painful and frequent insulin injections or the use of mechanical insulin pumps. There is no cure.

The researchers noted in their paper that existing therapies for diabetes increase insulin secretion without regard for insulin granule age. “Accordingly,” they wrote, “these approaches are effective only for a short period.”

Insulin is produced by beta cells of the pancreas and stored in insulin granules, which are then organized into pools and finally secreted into the bloodstream. Pools of young insulin granules are preferred for secretion over pools of old ones, for reasons that remain unclear.

The scientists whose work was published in JBC wanted to learn more about how pancreatic cells can distinguish between pools with young or old insulin granules.

“Current therapeutics do not take the existence of pools into consideration,” said Melkam Kebede, an assistant professor at the University of Sydney who oversaw sthe study. “By evolution, the (pancreatic) cells have determined what to secrete and what not. Understanding the mechanism and molecular differences between the pools definitely is going to lead us into something meaningful.”

In their paper, the researchers describe a technique they developed to distinguish younger insulin granules from older ones. The scientists placed a fluorescent protein, called Syncollin-dsRedE5TIMER, into newly created insulin granules and used a laser and detector to visualize that marker. In younger granules, the marker emits a green fluorescent light; as granules get older, the marker begins to emit a red fluorescence.

The authors monitored the movements of and other changes in insulin granule pools and saw that, as predicted, both mouse and human cells preferentially release younger insulin granule pools into the bloodstream in response to glucose.

The researchers then set out to learn more about how pancreatic cells sort insulin granules into pools and release them when they are experiencing metabolic stress. The concern is that, when under stress, beta cells “could potentially lose their ability to distinguish young (granules) from old,” they wrote in their paper.

The team isolated beta cells from mice and simulated chronic low, high and normal blood sugar levels and found different glucose levels determine which pools of insulin granules, young or old, are secreted. They saw similar results when they used a common mouse model for Type 2 diabetes known as the db/db mouse. 

These findings are important, Kebede said, because “all the drugs that affect insulin secretion…just push any granule within the cell and eventually fail.”

Older insulin granules are naturally degraded in normally functioning beta cells, noted lead author Belinda Yau of the University of Sydney, but, in diabetes, a greater percentage of insulin granule pools are secreted, and there’s a mismatch in how they’re released. 

Being able to visualize insulin granules as they age and understanding better how their age affects their secretion may lead to the discovery of new biomarkers capable of indicating the development of diabetes and could help in the creation of therapies for Type 2 diabetes.

“If we can understand what makes up the granules and makes them do what they do, we can figure out a way to target the things that slow down or speed up their secretion,” Yau said.

Anand Rao

Anand Rao is an ASBMB science communicator.

Related articles

Part 1: ‘Aha moments’ essay contest honorable mentions
Miguel A. Contreras Hidalgo & Danielle Guarracino
From the journals: MCP
Nuala Del Piccolo & Laurel Oldach
Ceramides’ role in liver disease
Eleonora Scorletti & Rotonya M. Carr
Share your aha moments!
Allison Frick

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

Part 1: ‘Aha moments’ essay contest honorable mentions
Contest

Part 1: ‘Aha moments’ essay contest honorable mentions

May 6, 2021

To celebrate our three journals going open access, we invited readers to share their moments of discovery in science. Here are two honorable mentions.

From the journals: MCP
Journal News

From the journals: MCP

May 6, 2021

Using silver nanoparticles to target cancer. Glycosylation of SARS-CoV-2. Characterizing the glycan signature in tumor tissue. Read about recent papers in the journal Molecular & Cellular Proteomics.

Ceramides’ role in liver disease
Lipid News

Ceramides’ role in liver disease

May 5, 2021

These biologically active sphingolipids have roles in apoptosis, inflammation and insulin resistance, all critical factors in the pathogenesis of chronic liver disease.

Winners of the ‘aha moments’ essay contest
Contest

Winners of the ‘aha moments’ essay contest

May 4, 2021

To celebrate our three journals going open access, we invited readers to share their moments of discovery in science. Here are the first, second and third place winners.

The 17th-century cloth merchant who discovered the vast realm of tiny microbes
News

The 17th-century cloth merchant who discovered the vast realm of tiny microbes

May 2, 2021

Although untrained in science, Antonie van Leeuwenhoek became the greatest lens-maker of his day, discovered microscopic life forms and is known today as the “father of microbiology.”

Do kids really need to be vaccinated for COVID?
News

Do kids really need to be vaccinated for COVID?

May 1, 2021

Many experts argue that Covid-19 cannot be curbed without vaccinating children. But others aren’t so sure.