In This Issue of Diabetes

Edited by Helaine E. Resnick, PhD, MPH

Glucagon’s Long-Term Metabolic Effects Are Mediated in Part by Fibroblast Growth Factor 21

Data in this issue of Diabetes (p. 1453) show that fibroblast growth factor 21 (FGF21), a fasting-induced hormone secreted by the liver, is an important mediator of glucagon’s long-term metabolic actions. Glucagon is a counter-regulatory hormone to insulin and is released during periods of hypoglycemia to regulate glucose homeostasis. Glucagon agonism is considered to be a potentially promising avenue for the treatment of obesity and diabetes. Because native glucagon has molecular properties that make the hormone difficult to study, Habegger et al. developed a soluble, long-acting, selective glucagon receptor (GcgR) agonist (IUB288). When treated with IUB288, both chow-fed and DIO mice showed increased blood glucose. Chronic GcgR agonism resulted in lower levels of circulating cholesterol. In DIO mice, chronic GcgR activation also decreased body and fat mass while increasing both hepatic FGF21 expression and plasma FGF21. In isolated primary hepatocytes from wild-type (WT) mice, glucagon increased FGF21 expression in a dose-dependent manner. This effect was not seen in GcgR knockout hepatocytes. Chronic GcgR activation lowered circulating cholesterol and prevented fat mass accumulation in WT but not in FGF21–/– mice. To evaluate clinical relevance, investigators gave obese healthy subjects a 1 mg intramuscular injection of glucagon or placebo. Plasma FGF21 concentrations increased significantly in the human volunteers who received glucagon. Regarded as a whole, these results indicate that glucagon’s long-term metabolic effects on …

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This Article

  1. doi: 10.2337/db13-ti05 Diabetes vol. 62 no. 5 1355-1356
  1. Free via Open Access: OA