Match!

IL-6–Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion

Published on Jan 1, 2018in Diabetes7.20
· DOI :10.2337/db17-0637
Stephan Wueest15
Estimated H-index: 15
(Boston Children's Hospital),
Céline I. Laesser1
Estimated H-index: 1
(Boston Children's Hospital)
+ 6 AuthorsDaniel Konrad24
Estimated H-index: 24
(UZH: University of Zurich)
Abstract
We recently showed that interleukin (IL)-6-type cytokine signaling in adipocytes induces free fatty acid release from visceral adipocytes, thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by those means induce glucagon-like peptide 1 (GLP-1) secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high-fat diet for 12 weeks. Compared with control littermates, knockout mice showed impaired glucose tolerance and circulating leptin, GLP-1, and insulin levels were reduced. In line, leptin release from isolated adipocytes was reduced, and intestinal proprotein convertase subtilisin/kexin type 1 (Pcsk1) expression, the gene encoding PC1/3, which controls GLP-1 production, was decreased in knockout mice. Importantly, treatment with the GLP-1 receptor antagonist exendin 9-39 abolished the observed difference in glucose tolerance between control and knockout mice. Ex vivo, supernatant collected from isolated adipocytes of gp130 knockout mice blunted Pcsk1 expression and GLP-1 release from GLUTag cells. In contrast, glucose- and GLP-1-stimulated insulin secretion was not affected in islets of knockout mice. In conclusion, adipocyte-specific IL-6 signaling induces intestinal GLP-1 release to enhance insulin secretion, thereby counteracting insulin resistance in obesity.
  • References (43)
  • Citations (10)
References43
Newest
#1Huxing CuiH-Index: 14
#2Miguel LópezH-Index: 50
Last.Kamal RahmouniH-Index: 50
view all 3 authors...
78 CitationsSource
#1Adam P. Chambers (Novo Nordisk)H-Index: 16
#2Joyce E. Sorrell (UC: University of Cincinnati)H-Index: 11
Last.Darleen A. Sandoval (UM: University of Michigan)H-Index: 34
view all 12 authors...
61 CitationsSource
#1Shuyang Traub (University of Basel)H-Index: 5
#2Daniel T. Meier (University of Basel)H-Index: 2
Last.Marc Y. Donath (University of Basel)H-Index: 60
view all 14 authors...
28 CitationsSource
#1Lisa Cole Burnett (Columbia University)H-Index: 6
#2Alicja A. Skowronski (Columbia University)H-Index: 7
Last.Rudolph L. Leibel (Columbia University)H-Index: 76
view all 5 authors...
6 CitationsSource
16 CitationsSource
#1Eglantine Balland (Monash University, Clayton campus)H-Index: 10
#2Michael A. Cowley (Monash University, Clayton campus)H-Index: 46
46 CitationsSource
#1Stephan Wueest (Boston Children's Hospital)H-Index: 15
#2Flurin Item (Boston Children's Hospital)H-Index: 9
Last.Daniel Konrad (UZH: University of Zurich)H-Index: 24
view all 7 authors...
34 CitationsSource
#1Tadasuke Komori (Wakayama Medical University)H-Index: 13
#2Minoru TanakaH-Index: 41
Last.Yoshihiro Morikawa (Wakayama Medical University)H-Index: 31
view all 6 authors...
13 CitationsSource
#1Felicia Goldsmith (Louisiana State University Agricultural Center)H-Index: 4
#2Michael J. Keenan (Louisiana State University Agricultural Center)H-Index: 22
Last.Jianping Ye (Pennington Biomedical Research Center)H-Index: 55
view all 10 authors...
8 CitationsSource
#1KanjiYamaguchi (Kyoto Prefectural University of Medicine)H-Index: 21
#2Takeshi Nishimura (Kyoto Prefectural University of Medicine)H-Index: 9
Last.Yoshito Itoh (Kyoto Prefectural University of Medicine)H-Index: 9
view all 15 authors...
20 CitationsSource
Cited By10
Newest
#1Mara A. Dedual (UZH: University of Zurich)
#2Stephan Wueest (Boston Children's Hospital)H-Index: 15
Last.Daniel Konrad (UZH: University of Zurich)H-Index: 24
view all 4 authors...
Source
#1Jan-Bernd Funcke (UTSW: University of Texas Southwestern Medical Center)H-Index: 1
#2Philipp E. Scherer (UTSW: University of Texas Southwestern Medical Center)H-Index: 112
1 CitationsSource
#1Timothy S. Odermatt (UZH: University of Zurich)
#2Mara A. Dedual (UZH: University of Zurich)
Last.Daniel Konrad (UZH: University of Zurich)H-Index: 24
view all 5 authors...
Source
#1Saleh Afrasyabi (UI: University of Isfahan)
#2Syed Mohamad Marandi (UI: University of Isfahan)H-Index: 1
Last.Mehdi Kargarfard (UI: University of Isfahan)H-Index: 9
view all 3 authors...
Source
#1Fredrik Anesten (University of Gothenburg)H-Index: 8
#2Adrià Dalmau Gasull (University of Gothenburg)H-Index: 1
Last.John-Olov Jansson (University of Gothenburg)H-Index: 47
view all 12 authors...
Source
#1Du-Fang Ma (SDUTCM: Shandong University of Traditional Chinese Medicine)H-Index: 5
#2Yong Wang (SDUTCM: Shandong University of Traditional Chinese Medicine)H-Index: 1
Last.Xiao Li (SDUTCM: Shandong University of Traditional Chinese Medicine)H-Index: 4
view all 5 authors...
1 CitationsSource
#1Silvano Paternoster (Curtin University)H-Index: 3
#2Marco Falasca (Curtin University)H-Index: 40
2 CitationsSource
3 CitationsSource
#1Stephan Wueest (Boston Children's Hospital)H-Index: 15
#2Daniel Konrad (UZH: University of Zurich)H-Index: 24
3 CitationsSource
#1Charlotte Bayer Christiansen (UCPH: University of Copenhagen)H-Index: 6
#2Sara J. Lind (UCPH: University of Copenhagen)H-Index: 1
Last.Jens J. Holst (UCPH: University of Copenhagen)H-Index: 152
view all 11 authors...
1 CitationsSource
View next paperPancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice