Inhibiting the SNAP23 protein could lead to increased insulin secretion.
A recent study found that a protein involved with pancreatic secretions could potentially lead to more effective treatments for diabetes.
The protein SNAP23 plays a role in the pancreatic secretion of digestive enzymes and insulin. Scientists discovered that inhibiting this protein could potentially allow a more effective protein to take over, increasing insulin secretion, according to the study published by The Journal of Cell Biology.
Researchers believe that this could also potentially be a promising treatment for pancreatitis, as well.
Exocytosis is the movement of secretory molecules, including hormones and digestive enzymes, out of a cell, which is carried out by SNARE proteins. These proteins assist with the fusion of secretory vesicles with the plasma membrane.
There are 38 human SNARE proteins that have been discovered, and each has its own tissue expression and intracellular location, according to the study. SNAP25 is a SNARE protein that is involved with releasing neurotransmitters and insulin secretion from the pancreas. The SNAP23 protein is involved with vesicle fusion in nonneuronal cells, such as pancreatic cells, however, the protein’s role is dependent on cell type.
Both exocrine (enzyme secretion through ducts) and endocrine (hormone secretion into blood) functions are carried out by the pancreas. SNAP23 has been known to play a role in the endocrine function of pancreatic b cells and the exocrine function of acinar cells in vitro; however, in vivo, SNAP23’s role was previously unknown, according to the study.
The scientists created 2 mouse models with the SNAP23 gene removed from the pancreatic b or acinar cells. They discovered that mice without SNAP23 in acinar cells had reduced exocytosis of inactive digestive enzymes and less secretion of amylase.
Without SNAP23 in b cells, mice models had increased insulin secretion due to a change in how frequent insulin vesicles fused with the plasma membrane. These results suggest that SNAP23 may have 2 very different roles in the endocrine and exocrine processes of the pancreas, according to the study.
Since SNAP23 and SNAP25 are very similar proteins, they compete for binding with other proteins. SNAP23-contianing complexes are less stable compared with those bound to SNAP25, making them less ideal for binding. The SNAP23-containing complexes are less efficient at promoting vesicle fusion with the membrane, the researchers said.
In the study, the researchers showed that by disrupting SNAP23, more SNAP25-containing complexes were able to be created, subsequently improving hormone secretion and other processes involved with vesicle-membrane fusion.
Due to this finding, the scientists hypothesized that SNAP23 inhibitors could potentially be used to treat diabetes, since the increase of SNAP25-containing complexes would increase insulin secretion, according to the study.
Then, they screened compounds that may be effective, and found that MF286 targeted SNAP23 and did not bind to SNAP25. The compound was seen to increase insulin secretion both in vitro and in vivo. MF286 also improved glucose tolerance through inhibiting the formation of SNAP23-contining complexes.
Additionally, scientists found that MF286 reduced amylase secretion from pancreatic acinar cells, which could potentially be used to treat diabetes and pancreatitis.
If these findings hold true in humans, patients with diabetes or pancreatitis may have a new treatment option.