Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion During Acute Sepsis in Non-Diabetic Mice

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dc.contributor.authorWatanabe, Yoshio
dc.contributor.authorSingamsetty, Srikanth
dc.contributor.authorZou, Baobo
dc.contributor.authorGuo, Lanping
dc.contributor.authorStefanovski, Darko
dc.contributor.authorAlonso, Laura C
dc.contributor.authorGarcia-Ocana, Adolfo
dc.contributor.authorO'Donnell, Christopher P
dc.contributor.authorMcVerry, Bryan J
dc.date2023-05-17T11:55:27.000
dc.date.accessioned2023-05-23T04:44:38Z
dc.date.available2023-05-23T04:44:38Z
dc.date.issued2013-06-24
dc.date.submitted2015-06-18T07:37:50-07:00
dc.description.abstractObjectives The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support. Methods Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 µL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs. Measurements And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml). Conclusions The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia.
dc.description.commentsAt the time of publication, author Darko Stefanovski was affiliated with University of Southern California. Currently, he is a faculty member at the School of Veterinary Medicine at the University of Pennsylvania.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/48893
dc.legacy.articleid1137
dc.legacy.fields10.1371/journal.pone.0067716
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1137&context=vet_papers&unstamped=1
dc.rightsThis article is under a Creative Commons Attribution 4.0 license (https://creativecommons.org/licenses/by/4.0/). This license permits any user to download, print out, copy, archive, and distribute the article, so long as appropriate credit is given to the authors and source of the work.
dc.source.beginpagee67716
dc.source.issue132
dc.source.issue6
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitlePLoS ONE
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume8
dc.subject.otherMedical Biochemistry
dc.subject.otherMedical Pathology
dc.subject.otherMedicine and Health Sciences
dc.subject.otherVeterinary Medicine
dc.subject.otherVeterinary Pathology and Pathobiology
dc.titleExogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion During Acute Sepsis in Non-Diabetic Mice
dc.typeArticle
digcom.identifiervet_papers/132
digcom.identifier.contextkey7232738
digcom.identifier.submissionpathvet_papers/132
digcom.typearticle
dspace.entity.typePublication
relation.isAuthorOfPublication6f18de03-4ea6-4da8-b38a-5cb00310137e
relation.isAuthorOfPublication6f18de03-4ea6-4da8-b38a-5cb00310137e
relation.isAuthorOfPublication.latestForDiscovery6f18de03-4ea6-4da8-b38a-5cb00310137e
upenn.schoolDepartmentCenterDepartmental Papers (Vet)
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