Upregulation of Lysophosphatidylinositols in Diabetes: A Lipidomics Study

What is it about?

In this study, researchers identified new lipid species associated with the loss of pancreatic b-cells triggering diabetes. They measured lipid metabolites from prediabetic mice, patients after pancreaticoduodenectomy, and patients with T2D or high-risk of developing diabetes. They found that higher lysoPIs represent the major plasma lipid signature in prediabetic mice and humans associated with lower b-cell mass at an asymptomatic stage before diabetes onset. Elevated lysoPI levels correlated with glycemic control, fasting glycemia, and disposition index, but not with insulin resistance or obesity. Increased lysoPIs significantly correlated with HbA1c levels, which reflect glycemic control; with fasting glycemia; and disposition index and did not exhibit a correlation with insulin resistance or obesity. Additionally, addition of lysoPIs to INS-1E b-cells and isolated pancreatic islets enhanced glucose-stimulated insulin secretion. Overall, circulating lysoPIs levels increase upon b-cell loss and exert insulinotropic effects on b-cells.

Featured Image

Why is it important?

This research is important because it identifies new lipid species associated with the loss of pancreatic b-cells triggering diabetes. By using lipidomics measurements on serum from prediabetic mice lacking b-cell prohibitin-2 and patients without previous history of diabetes but scheduled for pancreaticoduodenectomy, the study provides valuable insights into the circulating lipid signature associated with loss of functional b-cells. The findings could contribute to a better understanding of the underlying mechanisms of diabetes and potentially lead to the development of new diagnostic and therapeutic strategies. Key Takeaways: 1. The study identified higher lysoPIs as the major circulating lipids in prediabetic mice with controlled and progressive b-cell loss. 2. Elevated lysoPIs significantly correlated with HbA1c levels, fasting glycemia, and disposition index, but not with insulin resistance or obesity. 3. Increased lysoPIs enhance glucose-stimulated insulin secretion in b-cells, even when islets display secretory defects associated with diabetes. 4. The study suggests that lysoPIs could be a novel biomarker for diabetes and potentially have a role in the development of new diagnostic and therapeutic strategies.