Type I diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Current cell replacement therapies aim to produce insulin-producing beta cells using human pluripotent stem cells.

In a new study, researchers from the University of Copenhagen in Denmark found signals that determine the fate of immature cells in the pancreas, namely, the pancreatic progenitor. They found that within the developing pancreas, these pancreatic progenitor cells are highly mobile and their fate is affected by their surroundings. This is to say, exposure to specific extracellular matrix components determines their ultimate fate. This breakthrough discovery will help treat type 1 diabetes with islet beta cells produced by stem cells. The results of the study were published online November 28, 2018 in the journal Nature, entitled "Mechanosignalling via integrins directs fate decisions of pancreatic progenitors". The author of the paper is Professor Henrik Semb, Managing Director of the Stem Cell Biology Center at the Novo Nordisk Foundation of the University of Copenhagen. The first author of the paper is Anant Mamidi and Christy Prawiro of the University of Copenhagen.

Extracellular matrix determines the fate of pancreatic progenitor cells

Progenitor cells are similar to stem cells because they are capable of self-renewal and differentiation into mature cell types. However, their ability to self-renew is usually limited compared to stem cells. The dynamic behavior of progenitor cells during organ formation makes it difficult to study them. To overcome this obstacle, these researchers inoculated pancreatic progenitor cells derived from human stem cells onto glass slides with different matrix proteins. In this way, they were able to study how each pancreatic progenitor responds to its surroundings without affecting adjacent cells. Surprisingly, they found that the interaction between different extracellular matrix components alters the mechanical forces within the pancreatic progenitor cells. These mechanical forces are produced by the interaction between the extracellular matrix located outside the cell and the actin cytoskeleton located inside the cell.

Pancreatic progenitor cells are capable of producing pancreatic endocrine cells and pancreatic duct cells. Pancreatic endocrine cells include all hormone-producing cells in the pancreas, such as insulin-producing beta cells located inside the islets and glucagon-producing alpha cells, whereas pancreatic ductal cells are epithelial cells located on the inner wall of the pancreatic duct. In this new study, the researchers found that exposure to the extracellular matrix laminin reduces intracellular mechanical forces and directs pancreatic progenitor cells to produce pancreatic endocrine cells. Conversely, exposure to fibronectin increases intracellular mechanical force, thereby promoting pancreatic progenitor cells to produce pancreatic ductal cells.

Application of this newly identified differentiation mechanism of pancreatic progenitor cells

By analyzing in detail the differentiation mechanisms of pancreatic progenitor cells, these researchers revealed the molecular details of the corresponding signaling pathways that have a physiologically important role in understanding pancreatic development in vivo. Semb explains, “We are now able to replace a large number of empirically derived substances with small molecule inhibitors that target specific components of this newly identified mechanical signaling pathway, especially during the current cell differentiation process. The mode of action is largely unknown."

Through this new strategy, insulin-producing beta cells can now be made more economically and reliably using human pluripotent stem cells for future use in the treatment of diabetes. Semb said, “Our findings opened up new areas because it explains how pluripotent progenitors differentiate into different cell types during organogenesis. It also provides us with the process of rebuilding this process in the laboratory, so as to more accurately produce cells that are lost or damaged in serious diseases such as type 1 diabetes and neurodegenerative diseases for future cell replacement therapy."

Peptides related to diabetes treatment
Great efforts have been made by generations of scientists in the hope of finding an appropriate treatment for diabetes. Peptide-based diabetes mellitus treatment is leading a revolution in the treatment of diabetes due to their multi-functional properties. And till now, a couple of stable GLP-1 agonists have been approved by FDA as a new class of diabetic drugs, including Liraglutide, Albiglutide and Dulaglutide, etc. Other types of peptides involved with diabetes research are also listed as below:

 Amylins (IAPP) and Fragments
Ghrelin Peptides
 Insulin
 C-Peptides
Chromogranin A / Pancreastatin
 Exendins and Fragments
 Glucagons and Glucagon-Like Peptides (GLP-1 / GLP-2)
 Gastric Inhibitory Polypeptide and Fragments
Insulin-Like Growth Factors (IGF), Fragments & Related Peptides

Author's Bio: 

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