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Effect of high fat diet on gene expression in pancreatic islet associated macrophages

ABSTRACT: We have exploited islet-associated macrophages (IAMs) as a model of resident macrophage function, focusing on more physiological conditions than the commonly used extremes of M1 (inflammation) versus M2 (tissue-remodelling) polarization. Under steady-state, murine IAMs are metabolically poised between aerobic glycolysis and oxidative phosphorylation, and thereby exert a brake on glucose-stimulated insulin secretion (GSIS). This is underpinned by epigenetic remodelling via the metabolically-regulated histone demethylase Kdm5a. Conversely, GSIS is enhanced by engaging Axl receptors on IAMs, or by augmenting their oxidation of glucose. Following high-fat feeding, efferocytosis is stimulated in IAMs in conjunction with Mertk and Tgfb receptor signalling. This impairs GSIS and potentially contributes to b-cell failure in pre-diabetes. Thus, IAMs serve as relays in many more settings than currently appreciated, fine-tuning insulin secretion in response to dynamic changes in the external environment. Intervening in this nexus might represent a means of preserving b-cell function during metabolic disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE226713 | GEO | 2023/04/26

REPOSITORIES: GEO

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