Loss of Interleukin‐6 Blunts Glucagon Secretion During Hypoglycemia

Abstract

We have shown that the glucagon response to lipopolysaccharide was blunted in interleukin 6 knock‐out (IL6 KO) mice. In this study, we investigated the effects of a non‐inflammatory stimulus on the glucagon response in IL6 KO mice. Chronically catheterized conscious male mice (C57BL6/j; 8–10 weeks old) were subjected to a 5‐hr fast, after which hypoglycemic clamps were performed. Insulin (10mU/kg/min) and glucose were infused to maintain arterial blood glucose between 50–70 mg/dl. Initial glucagon response was blunted in the IL6 KO mice compared to the wild‐type (WT) (213±74 vs. 867±294, pg/ml). Epinephrine was significantly higher in the IL6 KO mice compared to WT (1049±298 vs. 308±123, pg/ml). There was no significant difference in the insulin concentration, corticosteroids, and norepinephrine response. Perifused islets were also stimulated in vitro using hypoglycemia, epinephrine and arginine. There was no significant difference in the glucagon response between the islets from WT and IL6 KO mice. In summary, IL6 KO mice have an impaired glucagon response when subjected to a non‐ inflammatory stimulus in vivo, but the blunted response is not observed in islets in vitro. Since the epinephrine response to hypoglycemia was not blunted, IL6 may play a role in augmenting pancreatic autonomic tone during hypoglycemia. Funding: DK043748, DK078188 and DK059637