Inflammation and insulin resistance are characteristics of endotoxemia. While the role of interleukin-6 (IL-6) in insulin resistant states has been characterized, little is known of its role in the metabolic response to inflammation. To study the role of IL-6, conscious chronically catheterized mice were used. Five days prior to being studied, catheters were implanted in the carotid artery and jugular vein. After a 5 h fast, E.coli (250 microgram/mouse) LPS was injected in IL6-/- (KO; n=13), IL6+/- (HET; n=9), and IL-6+/+ (WT; n=10) littermates. The IL-6 response to LPS was simulated in an additional group of KO mice (KO+IL6; n=10). Glucose turnover (Ra) was assessed using 3-[3H]-D-glucose. IL-6 increased similarly in WT and HET (15±0.7 and 14±0.5 ng/ml) 4h after LPS and was undetectable in KO. IL-6 replacement in KO restored circulating IL-6 to levels observed in the WT group (14±0.3 ng/ml). WT was the only group to experience an early rise in tumor necrosis factor-alpha (TNF-alpha). Interleukin-1beta (IL-1beta) was similar in all groups. KO exhibited a more profound hyperglycemia 30 min after LPS injection and no apparent hypoglycemia at 4h (95±5 mg/dl). Glucose levels in KO+IL6, while decreased (93±4 mg/dl) at 4h, remained higher than WT. Ra was not altered. In summary, the absence of IL-6 protected against LPS induced hypoglycemia. Acute restoration of the IL-6 response to LPS did not potentiate hypoglycemia. Thus, while IL-6 promotes glucose intolerance in insulin resistant states, IL-6 promotes hypoglycemia during inflammation.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07282005-151919 |
| Date | 29 July 2005 |
| Creators | Tweedell, Andrea Donielle |
| Contributors | Owen McGuinness, Mary Courtney Moore, David Wasserman, Masakazu Shiota |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07282005-151919/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0026 seconds