Macropinocytosis is decreased in diabetic mouse macrophages and is regulated by AMPK

Christopher B. Guest, Kenneth S. Chakour, Gregory G. Freund

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Macrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized by metabolic abnormalities and altered immune function. Here we examine the influence of diabetes on macropinocytosis in primary mouse macrophages and in an in vitro diabetes model. Results: The data demonstrate that peritoneal MΦs from diabetic (db/ db) mice had reduced macropinocytosis when compared to MΦs from non-diabetic (db/+) mice. Additionally, MΦs cultured in hyperglycemic conditions were less adept at macropinocytosis than those cultured in low glucose. Notably, AMP-activated protein kinase (AMPK) activity was decreased in MΦs cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1- β-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis. Conclusion: Taken together, these findings indicate that MΦs from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MΦs and suggest that increasing AMPK activity in diabetic MΦs could improve innate immunity and decrease susceptibility to infection.

Original languageEnglish (US)
Article number42
JournalBMC Immunology
Volume9
DOIs
StatePublished - Jul 30 2008

ASJC Scopus subject areas

  • Immunology

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