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Role of fibroblast growth factor 19 in the control of glucose homeostasis

Schaap, Frank G.

Current Opinion in Clinical Nutrition & Metabolic Care: July 2012 - Volume 15 - Issue 4 - p 386–391
doi: 10.1097/MCO.0b013e3283547171
CARBOHYDRATES: Edited by Luc Tappy and Bettina Mittendorfer

Purpose of review: Fibroblast growth factor 19 (FGF19) is a postprandial hormone released from the small intestine. FGF19 improves glucose tolerance when overexpressed in mice with impaired glucose tolerance or diabetes. This review summarizes the recent advances in our understanding of the biology of FGF19 and its role in glucose homeostasis, with emphasis on publications from 2010 to 2012.

Recent findings: Protein engineering was used to generate FGF19 protein variants that allowed the separation of its mitogenic and metabolic functions. Its cognate receptor in the liver (FGFR4) mediated the effects of FGF19 on proliferation and bile salt synthesis, while this receptor was dispensable for its effects on glucose homeostasis. New metabolic activities of FGF19 were uncovered. FGF19 signaling was shown to stimulate glycogen and protein synthesis, and inhibit gluconeogenesis. FGF19 employed signaling routes distinct from those used by insulin to regulate these pathways. Mice with genetic disruption of Fgf15 (the mouse FGF19 ortholog) were glucose intolerant but had normal insulin levels and normal insulin sensitivity. Reduced hepatic glycogen stores and elevated hepatic gluconeogenesis were observed in the knock-out mice under the conditions in which insulin signaling was active.

Summary: FGF19 signaling regulates glucose homeostasis in mice. The (patho)physiological role of FGF19 in glucose homeostasis in humans remains to be determined. Its novel insulin-mimetic actions, combined with the elimination of its mitogenic activity by protein engineering, make FGF19 an attractive candidate for the treatment of type 2 diabetes.

Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands

Correspondence to Frank G. Schaap, PhD, Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Meibergdreef 69-71, 1105 BK Amsterdam, the Netherlands. Tel: +31 20 566 8162; fax: +31 20 566 9190; e-mail: f.g.schaap@amc.uva.nl

© 2012 Lippincott Williams & Wilkins, Inc.