TY - JOUR
T1 - Lysophosphatidylinositols Are Upregulated After Human β-Cell Loss and Potentiate Insulin Release
AU - Jiméenez-Séanchez, Cecilia
AU - Sinturel, Flore
AU - Mezza, Teresa
AU - Loizides-Mangold, Ursula
AU - Montoya, Jonathan Paz
AU - Li, Lingzi
AU - di Giuseppe, Gianfranco
AU - Quero, Giuseppe
AU - Guessous, Idris
AU - Jornayvaz, François
AU - Schrauwen, Patrick
AU - Stenvers, Dirk Jan
AU - Alfieri, Sergio
AU - Giaccari, Andrea
AU - Berishvili, Ekaterine
AU - Compagnon, Philippe
AU - Bosco, Domenico
AU - Riezman, Howard
AU - Dibner, Charna
AU - Maechler, Pierre
AU - Jiménez-Sánchez, Cecilia
N1 - Publisher Copyright: © 2023 by the American Diabetes Association.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
KW - Animals
KW - Diabetes Mellitus, Type 2
KW - Glucose/pharmacology
KW - Humans
KW - Insulin
KW - Insulin, Regular, Human
KW - Insulin-Secreting Cells
KW - Islets of Langerhans
KW - Lysophospholipids
KW - Mice
KW - Prediabetic State
UR - http://www.scopus.com/inward/record.url?scp=85180714495&partnerID=8YFLogxK
U2 - 10.2337/db23-0205
DO - 10.2337/db23-0205
M3 - Article
C2 - 37862465
SN - 0012-1797
VL - 73
SP - 93
EP - 107
JO - Diabetes
JF - Diabetes
IS - 1
ER -