AI Article Synopsis
- Researchers have studied islet-associated macrophages (IAMs) as models for understanding how resident macrophages function under normal conditions, rather than the extreme inflammatory (M1) or tissue-repairing (M2) states.
- IAMs are shown to regulate insulin secretion by balancing between aerobic glycolysis and oxidative phosphorylation, partly due to changes in their genetic expression influenced by the enzyme Kdm5a.
- After eating a high-fat diet, IAMs increase their clearance of dead cells, which negatively affects insulin secretion and may lead to β-cell dysfunction in pre-diabetes; thus, targeting IAMs could help maintain insulin-producing cell health during metabolic disorders.
Article 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 remodeling) 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 remodeling 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 TGFβ receptor signaling. This impairs GSIS and potentially contributes to β-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 β-cell function during metabolic disease.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113792 | PMC |
| http://dx.doi.org/10.1016/j.isci.2023.106477 | DOI Listing |
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