SFEBES2026 Poster Presentations Neuroendocrinology and Pituitary (40 abstracts)
Involvement of GM3 gangliosides in acromegaly associated insulin resistance
Amy Coulden 1,2 , Priyankaa Patel 1 , Ying Di 1 , Ella Smith 1 , Warwick Dunn 3 , Catherine Winder 3 , Christian Ludwig 1 , Maria Makarova 1 , Niki Karavitaki 1,2 & Gabriela da Silva Xavier 1
1University of Birmingham, Birmingham, United Kingdom; 2Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; 3University of Liverpool, Liverpool, United Kingdom
Background: Acromegaly is a multi-system, multi-morbidity disease caused by a pituitary tumour that oversecretes growth hormone (GH); subsequently elevating levels of its effector hormone, insulin-like growth factor-1 (IGF-1). A significant number of patients with acromegaly develop insulin resistance and diabetes mellitus, the mechanism of which is not fully understood. GM3 gangliosides (GM3) have previously been mechanistically linked to insulin resistance in patients with diabetes mellitus.
Aim: We aimed to configure the role of GM3 in acromegaly-associated insulin resistance in 3T3-L1 adipocytes, a mouse adipocyte cell line.
Methods: 3T3-L1 adipocytes were exposed to GH (1 μM) and/or IGF-1 (1 μg/ml) for 48h. Insulin signalling was assessed by Western(mmuno)blot of AKT phosphorylation. Membrane order was assessed through measures of membrane polarisation by confocal microscopy of DI-4-ANEPPDHQ fluorescence. GM3 content in cellular extracts was measured by NMR spectroscopy. The expression of ST3GAL5 (which encodes for GM3 synthase, the enzyme responsible for GM3 synthesis) was assessed by qPCR.
Results: Exposure of 3T3-L1 adipocytes to elevated concentrations of GH and IGF-1 led to lowered phosphorylated AKT to total AKT levels, indicating impaired insulin signalling. This effect was associated with altered membrane fluidity (1.8± 0.1 fold, p≤0.01) and increased (1.75± 0.2 fold, p≤0.05) cellular levels of GM3 in the cells. Exposure to elevated GH concentrations also led to increased (1.4± 0.1 fold, p≤0.01) expression of ST3GAL5.
Conclusions: Taken together, these data indicate that exposure to GH and IGF-1, as seen in acromegaly, inhibits insulin signalling in 3T3-L1 adipocytes potentially via alterations in plasma membrane fluidity caused by increased GM3 content.
Volume 117
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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