ACSL1 and β-Cell Function: A Novel Pathway in the Pathophysiology of Type 2 Diabetes

Background

Type 2 diabetes (T2D) is a growing global health problem. While much research has focused on how insulin and glucose interact, the role of fatty acids in diabetes is less understood.

Hypothesis

Our research suggests that a protein called ACSL1 is important for insulin production in the pancreas. ACSL1 helps process fatty acids in cells, and we believe it plays a key role in keeping insulin-producing cells healthy and functioning properly.

Methods

We studied genetic data from 26,000 individuals and found that ACSL1 may affect diabetes risk. In lab experiments, we tested how turning ACSL1 “on” or “off” in pancreatic cells influences insulin production, energy use, and cell health. We also studied mice lacking ACSL1 in their insulin-producing cells and are using stem cells from diabetes patients to understand how ACSL1 affects human cells.

Results

When ACSL1 was turned off, insulin production decreased, and the cells struggled to generate energy properly. Mice without ACSL1 in their pancreatic cells had higher blood sugar and lower insulin levels. In diabetes-like conditions, ACSL1 levels naturally increased, helping cells produce more insulin.

Conclusions

ACSL1 is essential for insulin production and energy balance in pancreatic cells. Genetic differences in ACSL1 may influence a person’s risk of developing diabetes.

Importance

By understanding how ACSL1 functions, we may find new ways to predict who is at risk for diabetes before they develop high blood sugar. This research could also lead to new treatments that improve insulin production and prevent diabetes progression.