Scientific article

Lysophosphatidylinositols Are Upregulated After Human β-Cell Loss and Potentiate Insulin Release

Published inDiabetes, vol. 73, no. 1, p. 93-107
Publication date2024-01
First online date2023-10-20

In this study, we identified new lipid species associated with the loss of pancreatic β-cells triggering diabetes. We performed lipidomics measurements on serum from prediabetic mice lacking β-cell prohibitin-2 (a model of monogenic diabetes) patients without previous history of diabetes but scheduled for pancreaticoduodenectomy resulting in the acute reduction of their β-cell mass (∼50%), and patients with type 2 diabetes (T2D). We found lysophosphatidylinositols (lysoPIs) were the main circulating lipid species altered in prediabetic mice. The changes were confirmed in the patients with acute reduction of their β-cell mass and in those with T2D. Increased lysoPIs significantly correlated with HbA1c (reflecting glycemic control), fasting glycemia, and disposition index, and did not correlate with insulin resistance or obesity in human patients with T2D. INS-1E β-cells as well as pancreatic islets isolated from nondiabetic mice and human donors exposed to exogenous lysoPIs showed potentiated glucose-stimulated and basal insulin secretion. Finally, addition of exogenous lysoPIs partially rescued impaired glucose-stimulated insulin secretion in islets from mice and humans in the diabetic state. Overall, lysoPIs appear to be lipid species upregulated in the prediabetic stage associated with the loss of β-cells and that support the secretory function of the remaining β-cells.

  • Animals
  • Diabetes Mellitus, Type 2
  • Glucose / pharmacology
  • Humans
  • Insulin
  • Insulin, Regular, Human
  • Insulin-Secreting Cells
  • Islets of Langerhans
  • Lysophospholipids
  • Mice
  • Prediabetic State
Citation (ISO format)
JIMÉNEZ-SÁNCHEZ, Cecilia et al. Lysophosphatidylinositols Are Upregulated After Human β-Cell Loss and Potentiate Insulin Release. In: Diabetes, 2024, vol. 73, n° 1, p. 93–107. doi: 10.2337/db23-0205
Main files (1)
Article (Published version)
Secondary files (1)
ISSN of the journal0012-1797

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