Soluble interleukin-13rα1: a circulating regulator of glucose. Am J Physiol Endocrinol Metab 2017 Dec 01;313(6):E663-E671
Date
09/07/2017Pubmed ID
28874358Pubmed Central ID
PMC5814599DOI
10.1152/ajpendo.00168.2017Scopus ID
2-s2.0-85037052672 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
Soluble IL-13 receptor-α1, or sIL13rα1, is a soluble protein that binds to interleukin-13 (IL-13) that has been previously described in mice. The function of sIL13rα1 remains unclear, but it has been hypothesized to act as a decoy receptor for IL-13. Recent studies have identified a role for IL-13 in glucose metabolism, suggesting that a decoy receptor for IL-13 might increase circulating glucose levels. Here, we report that delivery of sIL13rα1 to mice by either gene transfer or recombinant protein decreases blood glucose levels. Surprisingly, the glucose-lowering effect of sIL13rα1 was preserved in mice lacking IL-13, demonstrating that IL-13 was not required for the effect. In contrast, deletion of IL-4 in mice eliminated the hypoglycemic effect of sIL13rα1. In humans, endogenous blood levels of IL13rα1 varied substantially, although there were no differences between diabetic and nondiabetic patients. There was no circadian variation of sIL13rα1 in normal human volunteers. Delivery of sIL13rα1 fused to a fragment crystallizable (Fc) domain provided sustained glucose lowering in mice on a high-fat diet, suggesting a potential therapeutic strategy. These data reveal sIL13rα1 as a circulating human protein with an unexpected role in glucose metabolism.
Author List
Rachmin I, O'Meara CC, Ricci-Blair EM, Feng Y, Christensen EM, Duffy JF, Zitting KM, Czeisler CA, Pancoast JR, Cannon CP, O'Donoghue ML, Morrow DA, Lee RTAuthor
Caitlin C. O'Meara PhD Associate Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Animals
Carbohydrate Metabolism
Female
Glucose
Humans
Hypoglycemic Agents
Interleukin-13 Receptor alpha1 Subunit
Interleukin-4
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Recombinant Proteins
Signal Transduction
Young Adult
