Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells

被引：708

作者：

Ellingsgaard, Helga ^{[1
,2
]}

Hauselmann, Irina ^{[1
,2
]}

Schuler, Beat ^{[3
,4
]}

Habib, Abdella M. ^{[5
,6
]}

Baggio, Laurie L. ^{[7
]}

Meier, Daniel T. ^{[1
,2
]}

Eppler, Elisabeth ^{[8
]}

Bouzakri, Karim ^{[9
]}

Wueest, Stephan ^{[4
,10
]}

Muller, Yannick D. ^{[11
]}

Hansen, Ann Maria Kruse ^{[12
]}

Reinecke, Manfred ^{[8
]}

Konrad, Daniel ^{[4
,10
]}

Gassmann, Max ^{[3
,4
]}

Reimann, Frank ^{[5
,6
]}

Halban, Philippe A. ^{[9
]}

Gromada, Jesper ^{[13
]}

Drucker, Daniel J. ^{[7
]}

Gribble, Fiona M. ^{[5
,6
]}

Ehses, Jan A. ^{[14
]}

Donath, Marc Y. ^{[1
,2
]}

机构：

[1] Univ Basel Hosp, Clin Endocrinol Diabet & Metab, CH-4031 Basel, Switzerland

[2] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland

[3] Univ Zurich, Inst Vet Physiol, Vetsuisse Fac, Zurich, Switzerland

[4] Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland

[5] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England

[6] Addenbrookes Hosp, Dept Clin Biochem, Cambridge, England

[7] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med, Toronto, ON M5G 1X5, Canada

[8] Univ Zurich, Inst Anat, Res Grp Neuroendocrine Immune Interact, Zurich, Switzerland

[9] Univ Geneva, Univ Med Ctr, Dept Genet Med & Dev, Geneva, Switzerland

[10] Univ Zurich, Univ Childrens Hosp, Div Pediat Endocrinol & Diabetol, Zurich, Switzerland

[11] Univ Geneva, Univ Med Ctr, Dept Surg, Cell Isolat & Transplantat Ctr, Geneva, Switzerland

[12] Novo Nordisk AS, Diabet Res Unit, Malov, Denmark

[13] Novartis Inst Biomed Res, Cardiovasc & Metab Dis Area, Cambridge, MA USA

[14] Univ British Columbia, Dept Surg, Fac Med, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada

来源：

NATURE MEDICINE | 2011年 / 17卷 / 11期

基金：

瑞士国家科学基金会; 英国惠康基金; 加拿大健康研究院;

关键词：

BETA-CELL; SKELETAL-MUSCLE; IN-VITRO; GLUCOSE-HOMEOSTASIS; BENEFICIAL ROLE; EXPRESSION; HORMONE; GLP-1; PROGLUCAGON; EXERCISE;

D O I：

10.1038/nm.2513

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.

引用

页码：1481 / U1500

页数：10

共 57 条

[1] Activity-induced GLP-1 release in lean and obese subjects
Adam, TCM
Westerterp-Plantenga, MS
[J]. PHYSIOLOGY & BEHAVIOR, 2004, 83 (03) : 459 - 466
[2] Role of leptin in the regulation of glucagon-like peptide-1 secretion
Anini, Y
Brubaker, PL
[J]. DIABETES, 2003, 52 (02) : 252 - 259
[3] HAMSTER PREPROGLUCAGON CONTAINS THE SEQUENCE OF GLUCAGON AND 2 RELATED PEPTIDES
BELL, GI
SANTERRE, RF
MULLENBACH, GT
[J]. NATURE, 1983, 302 (5910) : 716 - 718
[4] Unique Arrangement of α- and β-Cells in Human Islets of Langerhans
Bosco, Domenico
Armanet, Mathieu
Morel, Philippe
Niclauss, Nadja
Sgroi, Antonino
Muller, Yannick D.
Giovannoni, Laurianne
Parnaud, Geraldine
Berney, Thierry
[J]. DIABETES, 2010, 59 (05) : 1202 - 1210
[5] Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase
Carey, Andrew L.
Steinberg, Gregory R.
Macaulay, S. Lance
Thomas, Walter G.
Holmes, Anna G.
Ramm, Georg
Prelovsek, Oja
Hohnen-Behrens, Cordula
Watt, Matthew J.
James, David E.
Kemp, Bruce E.
Pedersen, Bente K.
Febbraio, Mark A.
[J]. DIABETES, 2006, 55 (10) : 2688 - 2697
[6] GLP-1 and appetite responses to a meal in lean and overweight adolescents following exercise
Chanoine, Jean-Pierre
MacKelvie, Kerry J.
Barr, Susan I.
Wong, Alfred C. K.
Meneilly, Graydon S.
Elahi, Dariush H.
[J]. OBESITY, 2008, 16 (01) : 202 - 204
[7] INCRETIN CONCEPT TODAY
CREUTZFELDT, W
[J]. DIABETOLOGIA, 1979, 16 (02) : 75 - 85
[8] Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy
De León, DD
Deng, SP
Madani, R
Ahima, RS
Drucker, DJ
Stoffers, DA
[J]. DIABETES, 2003, 52 (02) : 365 - 371
[9] Physical training may enhance β-cell function in type 2 diabetes
Dela, F
von Linstow, ME
Mikines, KJ
Galbo, H
[J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2004, 287 (05): : E1024 - E1031
[10] Prior in vitro exposure to GLP-1 with or without GIP can influence the subsequent beta cell responsiveness
Delmeire, D
Flamez, D
Moens, K
Hinke, SA
Van Schravendijk, C
Pipeleers, D
Schuit, F
[J]. BIOCHEMICAL PHARMACOLOGY, 2004, 68 (01) : 33 - 39

← 1 2 3 4 5 6 →