Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Kulaj, K; Harger, A; Bauer, M; Caliskan, ÖS; Gupta, TK; Chiang, DM; Milbank, E; Reber, J; Karlas, A; Kotzbeck, P; Sailer, DN; Volta, F; Lutter, D; Prakash, S; Merl-Pham, J; Ntziachristos, V; Hauner, H; Pfaffl, MW; Tschöp, MH; Müller, TD; Hauck, SM; Engel, BD; Gerdes, JM; Pfluger, PT; Krahmer, N; Stemmer, K.
Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo.
Nat Commun. 2023; 14(1): 709 Doi: 10.1038/s41467-023-36148-1 [OPEN ACCESS]
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Leading authors Med Uni Graz

Harger Alexandra

Co-authors Med Uni Graz

Kotzbeck Petra

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Abstract:

Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets. Notably, insulinotropic effects were restricted to AdEVs isolated from obese and insulin resistant, but not lean mice, which was consistent with differential protein loads and AdEV luminal morphologies. Likewise, in vivo pre-treatment with AdEVs from obese but not lean mice amplified insulin secretion and glucose tolerance in mice. This data suggests that secreted AdEVs can inform pancreatic β-cells about insulin resistance in adipose tissue in order to amplify GSIS in times of increased insulin demand.

Find related publications in this database (using NLM MeSH Indexing)

Mice - administration & dosage

Animals - administration & dosage

Insulin Secretion - administration & dosage

Insulin - metabolism

Glucose - metabolism

Insulin-Secreting Cells - metabolism

Obesity - metabolism

Adipocytes - metabolism

Extracellular Vesicles - metabolism

Islets of Langerhans - metabolism

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