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

Watanabe, Y and Singamsetty, S and Zou, B and Guo, L and Stefanovski, D and Alonso, LC and Garcia-Ocana, A and O'Donnell, CP and McVerry, BJ (2013) Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion during Acute Sepsis in Non-Diabetic Mice. PLoS ONE, 8 (6).

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Objectives: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. © 2013 Watanabe et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Watanabe, Y
Singamsetty, S
Zou, B
Guo, Llag53@pitt.eduLAG53
Stefanovski, D
Alonso, LC
Garcia-Ocana, A
O'Donnell, CP
McVerry, BJbjm42@pitt.eduBJM420000-0002-1175-4874
ContributionContributors NameEmailPitt UsernameORCID
Date: 24 June 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0067716
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Date Deposited: 15 Jul 2013 20:23
Last Modified: 29 Jan 2019 15:55


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