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. 2021 Jun 1;55(6):796-805.
doi: 10.1097/SHK.0000000000001683.

Hyper-Activation of Endogenous GLP-1 System to Gram-negative Sepsis Is Associated With Early Innate Immune Response and Modulated by Diabetes

Olga Bloch  1 , Sivan H Perl  2 , Tsilia Lazarovitch  3 , Dana Zelnik-Yovel  2 , Itamar Love  2 , Lior Mendel-Cohen  2 , Galina Goltsman  2 , Hadar Flor  2 , Micha J Rapoport  1   2
Affiliations

Hyper-Activation of Endogenous GLP-1 System to Gram-negative Sepsis Is Associated With Early Innate Immune Response and Modulated by Diabetes

Olga Bloch et al. Shock. .

Abstract

Background: Culture-positive gram-negative sepsis induces greater magnitude of early innate immunity /inflammatory response compared with culture-negative sepsis. We previously demonstrated increased activation of anti-inflammatory Glucagon Like Peptide-1 (GLP-1) hormone in initial phase of sepsis more pronounced in diabetes patients. However, whether GLP-1 system is hyperactivated during the early innate immune response to gram-negative sepsis and modulated by diabetes remains unknown.

Objectives: Total and active GLP-1, soluble Dipeptidyl peptidase 4 (sDPP-4) enzyme, and innate immunity markers presepsin (sCD14) and procalcitonin (PCT) in plasma were determined by ELISA on admission and after 2 to 4 days in 37 adult patients with and without type 2 diabetes and gram-negative or culture-negative sepsis of different severity.

Results: Severe but not non-severe sepsis was associated with markedly increased GLP-1 system response, which correlated with PCT and the organ dysfunction marker lactate. Culture-positive gram-negative bacteria but not culture-negative sepsis induced hyper-activation of GLP-1 system, which correlated with increased innate immune markers sCD14, PCT, and lactate. GLP-1 inhibitory enzyme sDPP-4 was down regulated by sepsis and correlated negatively with sCD14 in gram-negative sepsis. Diabetic patients demonstrated increased GLP-1 response but significantly weaker innate immune response to severe and gram-negative sepsis.

Conclusions: Early stage of gram-negative sepsis is characterized by endogenous GLP-1 system hyperactivity associated with over activation of innate immune response and organ dysfunction, which are modulated by diabetes. Total GLP-1 may be novel marker for rapid diagnosis of gram-negative sepsis and its severity.

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Conflict of interest statement

The authors report no conflicts of interest.

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