Novel pancreas-liver crosstalk: glucagon-follistatin interaction

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 389-408-Signaling Originating from Membrane Receptors
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-400
Peter Plomgaard*1, Claus Brandt2, Bente Klarlund Pedersen3, Philippe Halban4 and Karim Bouzakri5
1Rigshospitalet, Copenhagen, Denmark, 2Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Science, University of Copenhagen, Denmark, Copenhagen, Denmark, 3Rigshospitalet, copenhagen, Denmark, 4Geneva University, Geneve, Switzerland, 5Geneva University, Switzerland
Follistatin is a plasma protein with pleural regulatory properties, as it is known to bind and neutralise several members of the TGF-β family as activin A and myostatin. It has recently been demonstrated that plasma follistatin increases after prolonged fasting and acutely after an exercise bout. Exercise primarily increases follistatin in the liver. Both exercise and fasting are conditions with elevated glucagon. The aim of the present study was to investigate weather glucagon acts on the liver to produce and secrete follistatin and weather follistatin acutely impacts the pancreatic α-cells.

Methods: Mice, HepG2 and humans were challenged with glucagon and follistatin mRNA or protein measured. Primary rat beta-cells were used to explore the impact of 24 h exposure to follistatin (10 and 50 ng/mL) on apoptosis (TUNEL assay) and proliferation (BrdU incorporation). Human islets were exposed to 50 ng/mL of follistatin for different timing up to 24h in order to explore glucagon secretion. Data are mean +/- SE. 

Results: Mice injected with glucagon showed a 12.6-fold (p< 0.05) increase in liver follistatin mRNA 1 hour after administration compared to untreated mice. Glucagon increased HepG2 cells follistatin secretion to the media 2-fold compared to control (p<0.05). In humans (n=3) plasma follistatin increased 2 fold 4 hour after (p<0.05) a bolus of glucagon IV. Rat β-cells (n=4) treated with follistatin for 24h showed a decrease in apoptosis when compared to untreated cells (0.17 +/- 0.06 % and 0.42 +/- 0.04 % TUNEL positive cells for 10 and 50 ng/mL follistatin respectively vs. 0.87+/-0.8% for control). Proliferation was increased when compared to untreated cells (7.73+/-0.37 % and 6.27+/- 0.3 % BrdU positive cells for 10 and 50 ng/mL follistatin respectively vs. 4.0+/-0.17 % for control). In human islets treated with 50 ng/mL follistatin glucagon release (n=2) at 16.7 mM glucose was decreased 4-fold after 1 and 2 h follistatin treatment but unchanged after 24h, There was no effect of follistatin on stimulated glucagon secretion (2.8 mM glucose) at any time of treatment.

Conclusion: Our study indicates that glucagon induces hepatic follistatin expression and release. Furthermore that follistatin modulate the pancreatic glucagon response to hypoglycemia. Taken together these data suggest a novel liver pancreas crosstalk consisting of glucagon and follistatin.

Nothing to Disclose: PP, CB, BKP, PH, KB

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