Study Published in Nature Communications Shows How Reprogramming Pancreatic Acinar Cells into Insulin Producers May Be a Possible Treatment Approach for Diabetes
September 25, 2024
Researchers in the Esni Lab for Pancreas Research at UPMC Children’s Hospital of Pittsburgh are investigating a new method to address the shortage of insulin-producing cells in patients with diabetes. Their most recent study, published in Nature Communications, focuses on a method for reprogramming pancreatic acinar cells into insulin-producing β-like cells. This approach could provide new treatment options for individuals with diabetes, particularly those with significant β-cell loss.
Contributing to the study was Mohamed Saleh, MD, assistant professor of Pediatrics in the Division of Pediatric Endocrinology at UPMC Children’s and a researcher in the Gittes Lab.
The pancreas has two primary components: the endocrine part, which includes insulin-producing β-cells, and the exocrine part, which consists of acinar cells that produce digestive enzymes. Historically, the endocrine and exocrine pancreatic functions have been studied separately. Dr. Saleh’s research and that of the Esni and Gittes Labs aim to connect these functions by exploring the potential for acinar cells to be converted into β-like cells capable of producing insulin.
“Our focus is on linking the endocrine and exocrine parts of the pancreas to explore a potential new source of insulin-producing cells,” says Dr. Saleh. “For this study, we found that a specific subpopulation of acinar cells, particularly those surrounding the islets of Langerhans, show promise for this type of conversion.”
The Role of Focal Adhesion Kinase Inhibition
A key component of this research is the inhibition of focal adhesion kinase (FAK), an enzyme involved in various cellular functions, such as movement and survival. Dr. Saleh and colleagues used a FAK inhibitor, originally developed for cancer treatment, to spark the transformation of acinar cells into insulin-producing cells.
“Not all acinar cells are candidates for this transformation. It’s specifically the ones near the islets—what we call peri-islet acinar cells—that have the potential to convert into insulin-producing cells,” says Dr. Saleh. “These cells already exhibit some characteristics of both acinar and β-cells, which makes them more likely to respond to the FAK inhibitor and take on a new function.”
Study Overview and Findings
The study utilized small animal models and preliminary experiments in nonhuman primates to assess the effectiveness of the FAK inhibitor in promoting acinar cell conversion. In the mouse models, both healthy and diabetic mice were treated with the FAK inhibitor. In the diabetic cohort, where β-cells had been destroyed, the treatment led to some acinar cells beginning to produce insulin, which resulted in improved glucose control.
In addition to the mouse studies, early results from nonhuman primate models indicated that the treatment increased the number of insulin-producing cells.
"This work is still in its early stages," says Dr. Saleh. "We’ve only tested one subject so far, so we’re cautious about drawing conclusions until we have more data."
Implications for Diabetes Treatment
The team’s research suggests a potential new method for restoring insulin production in patients with significant β-cell loss. For Type 1 diabetes (T1D), this approach could reduce the dependence on insulin therapy, though it may not fully restore normal insulin levels.
"For patients with severe loss of β-cell mass, this treatment might not be a cure, but it could improve their condition by decreasing the amount of insulin they need," says Dr. Saleh.
For Type 2 diabetes or less severe manifestations of disease, the approach could potentially reduce or eliminate the need for insulin therapy by enhancing the body’s own endogenous insulin production.
"For these patients, it might be possible to achieve better control or even a cure," says Dr. Saleh. “A lot would depend on the individual characteristics of the patient, the functional capacity of the pancreas, and other factors that may be discovered as our research progresses.”
Future Research Goals
Several challenges in Dr. Saleh and colleague’s research persist, including ensuring that the FAK inhibitor specifically targets pancreatic cells without affecting other tissues or cellular processes, since FAK is essential in other cellular functions. Additionally, the exact mechanism by which FAK inhibition triggers the conversion of acinar cells is not yet fully understood by the team.
"The mechanism is still unclear," Dr. Saleh notes. "We believe it involves some genetic modulation, but we need to conduct more research to uncover the specific molecular mechanisms at work."
Before this approach can be translated into a clinical setting, more extensive studies, particularly in nonhuman primates, are necessary.
"We need more data from larger studies, and eventually, clinical trials, to see how this treatment can be applied to patients," says Dr. Saleh.
Read the full study using the reference link below to the open-access article.
Study Reference
Dahiya S*, Saleh M*, Rodriguez UA, et al. Acinar to β-like cell conversion through inhibition of focal adhesion kinase. Nat Commun. 2024; 15(1): 47972.
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