Nav: Home

Role of protein in pancreatic secretion suggests potential method for treating diabetes

December 08, 2016

Research reveals opposing roles for SNAP23 protein in the enzyme- and hormone-secretion functions of the pancreas; SNAP23 inhibitor increased insulin secretion in mice, suggesting potential use as a novel therapy for diabetes

Osaka, Japan - Movement of secretory molecules, such as hormones and digestive enzymes, out of the cell is known as exocytosis. This process is guided by SNARE proteins, which help the fusion of secretory vesicles with the plasma membrane. Thirty-eight human SNARE proteins have been identified, each with its own tissue expression and intracellular localization. One such SNARE, SNAP25, is particularly well characterized, being involved in the release of neurotransmitters as well as insulin secretion from pancreatic β cells. The closely related SNAP23 protein promotes vesicle fusion in many nonneuronal cells, including pancreatic cells, although its exact role depends on the cell type. The pancreas has both exocrine (digestive enzyme secretion through ducts) and endocrine (hormone secretion into the blood) functions, and SNAP23 was known to participate in the endocrine function of pancreatic β cells and the exocrine function of acinar cells in the laboratory. However, the in vivo function of SNAP23 was unknown.

To investigate this, a team of researchers led by Masataka Kunii, Akihiro Harada at Osaka University together with collaborators across Japan developed two mouse models with the Snap23 gene specifically knocked out in either β cells or acinar cells. The study was reported in The Journal of Cell Biology.

Loss of SNAP23 in acinar cells produced mice with reduced exocytosis of inactive digestive enzymes and lower secretion levels of the enzyme amylase. Conversely, loss of SNAP23 in β cells increased the frequency with which insulin vesicles fused with the plasma membrane, enhancing their secretion. These findings suggested opposite roles for SNAP23 in the endocrine and exocrine pancreas.

Because of the similarity between SNAP23 and SNAP25, the two SNAREs compete with each other for binding to other proteins. However, complexes containing SNAP23 are less stable than those with SNAP25, and less efficient at promoting vesicle fusion with the membrane. The researchers exploited this to show the disruption of SNAP23 enabled more SNAP25-containing complexes to form which enhanced processes, such as hormone secretion, that are reliant on vesicle-membrane fusion.

Extrapolating from this, the team predicted that SNAP23 inhibitors could be used as a novel treatment for diabetes by increasing insulin secretion. They screened a library of compounds and identified one, MF286, which bound specifically to SNAP23 but not SNAP25. MF286 was shown to increase insulin secretion both in vitro and in vivo and to improve glucose tolerance by blocking formation of the SNAP23-containing SNARE complex. It also reduced amylase secretion from pancreatic acinar cells, suggesting that it could be used to treat both pancreatitis and diabetes.
-end-
The article, "Opposing roles for SNAP23 in secretion in exocrine and endocrine pancreatic cells" was published in The Journal of Cell Biology at DOI: 10.1038/jcb.201604030

Osaka University

Related Diabetes Articles:

The role of vitamin A in diabetes
There has been no known link between diabetes and vitamin A -- until now.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
New cause of diabetes
Although insulin-producing cells are found in the endocrine tissue of the pancreas, a new mouse study suggests that abnormalities in the exocrine tissue could cause cell non-autonomous effects that promotes diabetes-like symptoms.
The Lancet Diabetes & Endocrinology: Reducing sugar content in sugar-sweetened drinks by 40 percent over 5 years could prevent 1.5 million cases of overweight and obesity in the UK and 300,000 cases of diabetes
A new study published in The Lancet Diabetes & Endocrinology journal suggests that reducing sugar content in sugar sweetened drinks (including fruit juices) in the UK by 40 percent over five years, without replacing them with any artificial sweeteners, could prevent 500,000 cases of overweight and 1 million cases of obesity, in turn preventing around 300,000 cases of type 2 diabetes, over two decades.
Breastfeeding lowers risk of type 2 diabetes following gestational diabetes
Women with gestational diabetes who consistently and continuously breastfeed from the time of giving birth are half as likely to develop type 2 diabetes within two years after delivery, according to a study from Kaiser Permanente published today in Annals of Internal Medicine.

Related Diabetes Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".