Role of tissue macrophages in the development of critical illness diabetes

Academic Article


  • Macrophage-derived factors, including TNF-α, are known as important inducers of insulin resistance. However, the role of macrophages in insulin resistance in the liver is unclear. Hyperglycemia and insulin resistance commonly occur following acute injuries or critical illness, referred to as "critical illness diabetes." In the present studies, the roles of macrophages in hepatic insulin resistance following surgical trauma and hemorrhage were investigated. Intravenous administration of gadolinium chloride or clodronate-liposome resulted in depletion of macrophages in both liver and spleen of rats. Macrophage depletion by either gadolinium chloride or clodronate-liposome did not prevent the development of trauma and hemorrhage-induced insulin resistance in the liver of rats, as indicated by impaired hepatic insulin signaling following a 90-minute hemorrhage period. Similarly, hepatic insulin resistance still developed in rats after removal of the spleen (splenectomy). In contrast, macrophage depletion significantly reversed the hepatic insulin resistance several hours later, following resuscitation. As a comparison, splenectomy resulted in improvement in hepatic insulin signaling following resuscitation, but to a lesser extent, suggesting that both liver and spleen resident macrophages have a role in the continuation of hepatic insulin resistance following resuscitation. These studies demonstrated that the initial development of insulin resistance in liver is macrophage-independent in a rodent model of critical illness diabetes, whereas both liver and spleen macrophages have a role in the later maintenance of the insulin-resistant state, following resuscitation. Abbreviations: CLD-lipo-clodronate-liposomeGdCl3-gadolinium chlorideIR-insulin receptorIRS-insulin receptor substrateIKK-inhibitory κB kinaseJNK-c-Jun N-terminal kinaseTH-trauma and hemorrhageT-trauma alone.
  • Published In

  • Shock  Journal
  • Digital Object Identifier (doi)

    Author List

  • Jiang S; Gavrikova TA; Sharifov OF; Messina JL
  • Start Page

  • 70
  • End Page

  • 76
  • Volume

  • 37
  • Issue

  • 1