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Adipocyte PI3K links adipostasis with baseline insulin secretion at fasting through an adipoincretin effect

Authors :
Barbara Becattini
Angela Molinaro
Marcus Henricsson
Jan Borén
Giovanni Solinas
Source :
Cell Reports, Vol 43, Iss 5, Pp 114132- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Insulin-PI3K signaling controls insulin secretion. Understanding this feedback mechanism is crucial for comprehending how insulin functions. However, the role of adipocyte insulin-PI3K signaling in controlling insulin secretion in vivo remains unclear. Using adipocyte-specific PI3Kα knockout mice (PI3KαAdQ) and a panel of isoform-selective PI3K inhibitors, we show that PI3Kα and PI3Kβ activities are functionally redundant in adipocyte insulin signaling. PI3Kβ-selective inhibitors have no effect on adipocyte AKT phosphorylation in control mice but blunt it in adipocytes of PI3KαAdQ mice, demonstrating adipocyte-selective pharmacological PI3K inhibition in the latter. Acute adipocyte-selective PI3K inhibition increases serum free fatty acid (FFA) and potently induces insulin secretion. We name this phenomenon the adipoincretin effect. The adipoincretin effect operates in fasted mice with increasing FFA and decreasing glycemia, indicating that it is not primarily a control system for blood glucose. This feedback control system defines the rates of adipose tissue lipolysis and chiefly controls basal insulin secretion during fasting.

Details

Language :
English
ISSN :
22111247
Volume :
43
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.3dbafa545ff34e0d8fa05f80be9e0922
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2024.114132