Insulin acutely activates metabolism of primary human monocytes and promotes a proinflammatory phenotype

Jacqueline M. Ratter, Julia I.P. van Heck, Hanne M.M. Rooijackers, Henry J. Jansen, Pleun C.M. van Poppel, Cees J. Tack, Rinke Stienstra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Increased glycolysis is a metabolic trait of activated innate immune cells and supports functional changes including cytokine production. Insulin drives glycolysis in nonimmune cells, yet its metabolic effects on human innate immune cells remain unexplored. Potential effects of insulin on immune cell metabolism may occur acutely after a postprandial increase in plasma insulin levels or as a consequence of chronically elevated insulin levels as observed in obese insulin-resistant individuals and patients with diabetes. Here, we investigated the effects of acute and chronic exposure to insulin on metabolism and function of primary human monocytes. Insulin acutely activated the PI3K/Akt/mTOR pathway in monocytes and increased both oxygen consumption and glycolytic rates. Functionally, acute exposure to insulin increased LPS-induced IL-6 secretion and reactive oxygen species production. To model chronically elevated insulin levels in patients with diabetes, we exposed monocytes from healthy individuals for 24 h to insulin. Although we did not find any changes in expression of metabolic genes that are regulated by insulin in non-immune cells, chronic exposure to insulin increased LPS-induced TNFα production and enhanced MCP-1-directed migration. Supporting this observation, we identified a positive correlation between plasma insulin levels and macrophage numbers in adipose tissue of overweight individuals. Altogether, insulin acutely activates metabolism of human monocytes and induces a shift toward a more proinflammatory phenotype, which may contribute to chronic inflammation in patients with diabetes.

Original languageEnglish
JournalJournal of Leukocyte Biology
DOIs
Publication statusE-pub ahead of print - 21 Jan 2021

Keywords

  • cytokines
  • diabetes
  • glycolysis
  • immunometabolism

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