Macropinocytosis is decreased in diabetic mouse macrophages and is regulated by AMPK.
BACKGROUND
Macrophages (MPhis) 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 MPhis from diabetic (db/db) mice had reduced macropinocytosis when compared to MPhis from non-diabetic (db/+) mice. Additionally, MPhis 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 MPhis cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1-beta-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis.


CONCLUSIONS
Taken together, these findings indicate that MPhis from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MPhis and suggest that increasing AMPK activity in diabetic MPhis could improve innate immunity and decrease susceptibility to infection.
Guest
Christopher B
CB
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, USA. cguest@uiuc.edu
Chakour
Kenneth S
KS
Freund
Gregory G
GG
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects / Q000276:immunology; D005947:Glucose / Q000172:deficiency / Q000276:immunology / Q000494:pharmacology; D006943:Hyperglycemia / Q000276:immunology; D007109:Immunity / Q000187:drug effects; D020738:Leptin / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010873:Pinocytosis / Q000187:drug effects / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology
D020738:Leptin; D011720:Pyrazoles; D011743:Pyrimidines; D012263:Ribonucleosides; C516138:dorsomorphin; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D055372:AMP-Activated Protein Kinases; D005947:Glucose