Insulin Secretion Depends on Intra-islet Glucagon Signaling

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Insulin Secretion Depends on Intra-islet Glucagon Signaling. / Svendsen, Berit; Larsen, Olav; Gabe, Maria Buur Nordskov; Christiansen, Charlotte Bayer; Rosenkilde, Mette M; Drucker, Daniel J; Holst, Jens Juul.

In: Cell Reports, Vol. 25, No. 5, 2018, p. 1127-1134.E2.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Svendsen, B, Larsen, O, Gabe, MBN, Christiansen, CB, Rosenkilde, MM, Drucker, DJ & Holst, JJ 2018, 'Insulin Secretion Depends on Intra-islet Glucagon Signaling', Cell Reports, vol. 25, no. 5, pp. 1127-1134.E2. https://doi.org/10.1016/j.celrep.2018.10.018

APA

Svendsen, B., Larsen, O., Gabe, M. B. N., Christiansen, C. B., Rosenkilde, M. M., Drucker, D. J., & Holst, J. J. (2018). Insulin Secretion Depends on Intra-islet Glucagon Signaling. Cell Reports, 25(5), 1127-1134.E2. https://doi.org/10.1016/j.celrep.2018.10.018

Vancouver

Svendsen B, Larsen O, Gabe MBN, Christiansen CB, Rosenkilde MM, Drucker DJ et al. Insulin Secretion Depends on Intra-islet Glucagon Signaling. Cell Reports. 2018;25(5):1127-1134.E2. https://doi.org/10.1016/j.celrep.2018.10.018

Author

Svendsen, Berit ; Larsen, Olav ; Gabe, Maria Buur Nordskov ; Christiansen, Charlotte Bayer ; Rosenkilde, Mette M ; Drucker, Daniel J ; Holst, Jens Juul. / Insulin Secretion Depends on Intra-islet Glucagon Signaling. In: Cell Reports. 2018 ; Vol. 25, No. 5. pp. 1127-1134.E2.

Bibtex

@article{7b6bd9cbf73b417ba7a64f12b6d33420,

title = "Insulin Secretion Depends on Intra-islet Glucagon Signaling",

abstract = "The intra-islet theory states that glucagon secretion is suppressed when insulin secretion is stimulated, but glucagon's role in intra-islet paracrine regulation is controversial. This study investigated intra-islet functions of glucagon in mice. We examined glucagon-induced insulin secretion using isolated perfused pancreata from wild-type, GLP-1 receptor (GLP-1R) knockout, diphtheria toxin-induced proglucagon knockdown, β cell-specific glucagon receptor (Gcgr) knockout, and global Gcgr knockout (Gcgr −/−) mice. We found that glucagon stimulates insulin secretion through both Gcgr and GLP-1R. Moreover, loss of either Gcgr or GLP-1R does not change insulin responses, whereas combined blockage of both receptors significantly reduces insulin secretion. Active GLP-1 is identified in pancreatic perfusate from Gcgr −/− but not wild-type mice, suggesting that β cell GLP-1R activation results predominantly from glucagon action. Our results suggest that combined activity of glucagon and GLP-1 receptors is essential for β cell secretory responses, emphasizing a role for paracrine intra-islet glucagon actions to maintain appropriate insulin secretion. Glucose-stimulated insulin secretion can be regulated by glucagon and GLP-1 receptors on paracrine β-cells. Svendsen et al. find that complete blockade of glucagon signaling in islets severely limits insulin secretion but establish that paracrine glucagon signaling involves both the glucagon and GLP-1 receptors. ",

keywords = "exendin(9-39), GLP-1 receptor, glucagon, glucagon receptor, Intra-islet communication, perfused mouse pancreas",

author = "Berit Svendsen and Olav Larsen and Gabe, {Maria Buur Nordskov} and Christiansen, {Charlotte Bayer} and Rosenkilde, {Mette M} and Drucker, {Daniel J} and Holst, {Jens Juul}",

year = "2018",

doi = "10.1016/j.celrep.2018.10.018",

language = "English",

volume = "25",

pages = "1127--1134.E2",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "5",

}

RIS

TY - JOUR

T1 - Insulin Secretion Depends on Intra-islet Glucagon Signaling

AU - Svendsen, Berit

AU - Larsen, Olav

AU - Gabe, Maria Buur Nordskov

AU - Christiansen, Charlotte Bayer

AU - Rosenkilde, Mette M

AU - Drucker, Daniel J

AU - Holst, Jens Juul

PY - 2018

Y1 - 2018

N2 - The intra-islet theory states that glucagon secretion is suppressed when insulin secretion is stimulated, but glucagon's role in intra-islet paracrine regulation is controversial. This study investigated intra-islet functions of glucagon in mice. We examined glucagon-induced insulin secretion using isolated perfused pancreata from wild-type, GLP-1 receptor (GLP-1R) knockout, diphtheria toxin-induced proglucagon knockdown, β cell-specific glucagon receptor (Gcgr) knockout, and global Gcgr knockout (Gcgr −/−) mice. We found that glucagon stimulates insulin secretion through both Gcgr and GLP-1R. Moreover, loss of either Gcgr or GLP-1R does not change insulin responses, whereas combined blockage of both receptors significantly reduces insulin secretion. Active GLP-1 is identified in pancreatic perfusate from Gcgr −/− but not wild-type mice, suggesting that β cell GLP-1R activation results predominantly from glucagon action. Our results suggest that combined activity of glucagon and GLP-1 receptors is essential for β cell secretory responses, emphasizing a role for paracrine intra-islet glucagon actions to maintain appropriate insulin secretion. Glucose-stimulated insulin secretion can be regulated by glucagon and GLP-1 receptors on paracrine β-cells. Svendsen et al. find that complete blockade of glucagon signaling in islets severely limits insulin secretion but establish that paracrine glucagon signaling involves both the glucagon and GLP-1 receptors.

AB - The intra-islet theory states that glucagon secretion is suppressed when insulin secretion is stimulated, but glucagon's role in intra-islet paracrine regulation is controversial. This study investigated intra-islet functions of glucagon in mice. We examined glucagon-induced insulin secretion using isolated perfused pancreata from wild-type, GLP-1 receptor (GLP-1R) knockout, diphtheria toxin-induced proglucagon knockdown, β cell-specific glucagon receptor (Gcgr) knockout, and global Gcgr knockout (Gcgr −/−) mice. We found that glucagon stimulates insulin secretion through both Gcgr and GLP-1R. Moreover, loss of either Gcgr or GLP-1R does not change insulin responses, whereas combined blockage of both receptors significantly reduces insulin secretion. Active GLP-1 is identified in pancreatic perfusate from Gcgr −/− but not wild-type mice, suggesting that β cell GLP-1R activation results predominantly from glucagon action. Our results suggest that combined activity of glucagon and GLP-1 receptors is essential for β cell secretory responses, emphasizing a role for paracrine intra-islet glucagon actions to maintain appropriate insulin secretion. Glucose-stimulated insulin secretion can be regulated by glucagon and GLP-1 receptors on paracrine β-cells. Svendsen et al. find that complete blockade of glucagon signaling in islets severely limits insulin secretion but establish that paracrine glucagon signaling involves both the glucagon and GLP-1 receptors.

KW - exendin(9-39)

KW - GLP-1 receptor

KW - glucagon

KW - glucagon receptor

KW - Intra-islet communication

KW - perfused mouse pancreas

U2 - 10.1016/j.celrep.2018.10.018

DO - 10.1016/j.celrep.2018.10.018

M3 - Journal article

C2 - 30380405

VL - 25

SP - 1127-1134.E2

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

ER -

ID: 204461637

Department of Biomedical Sciences