USF-LVHN SELECT
Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide by enteral dextrose improves glucose homeostasis and inflammation in murine endotoxemia.
Publication/Presentation Date
3-1-2018
Abstract
Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis. We administered IV or enteral dextrose to 10-week-old male C57BL/6J mice exposed to bacterial endotoxin and measured incretin hormone release, glucose disposal, and proinflammatory cytokine production. Compared with IV administration, enteral dextrose increased circulating levels of the incretin hormone glucose-dependent insulinotropic peptide (GIP) associated with increased insulin release and insulin sensitivity, improved mean arterial pressure, and decreased proinflammatory cytokines in endotoxemic mice. Exogenous GIP rescued glucose metabolism, improved blood pressure, and increased insulin release in endotoxemic mice receiving IV dextrose, whereas pharmacologic inhibition of GIP signaling abrogated the beneficial effects of enteral dextrose. Thus, stimulation of endogenous GIP secretion by early enteral dextrose maintains glucose homeostasis and attenuates the systemic inflammatory response in endotoxemic mice and may provide a therapeutic target for improving glycemic control and clinical outcomes in patients with sepsis.
Volume
193
First Page
1
Last Page
12
ISSN
1878-1810
Published In/Presented At
Shah, F. A., Singamsetty, S., Guo, L., Chuan, B. W., McDonald, S., Cooper, B. A., O'Donnell, B. J., Stefanovski, D., Wice, B., Zhang, Y., O'Donnell, C. P., & McVerry, B. J. (2018). Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide by enteral dextrose improves glucose homeostasis and inflammation in murine endotoxemia. Translational research : the journal of laboratory and clinical medicine, 193, 1–12. https://doi.org/10.1016/j.trsl.2017.11.001
Disciplines
Medical Education | Medicine and Health Sciences
PubMedID
29222967
Department(s)
USF-LVHN SELECT Program, USF-LVHN SELECT Program Students
Document Type
Article