GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells

被引：92

作者：

El, K. ^{[1
]}

Gray, S. M. ^{[1
]}

Capozzi, M. E. ^{[1
]}

Knuth, E. R. ^{[2
]}

Jin, E. ^{[2
]}

Svendsen, B. ^{[1
]}

Clifford, A. ^{[1
]}

Brown, J. L. ^{[1
]}

Encisco, S. E. ^{[1
]}

Chazotte, B. M. ^{[1
]}

Sloop, K. W. ^{[3
]}

Nunez, D. J. ^{[1
]}

Merrins, M. J. ^{[2
]}

D'Alessio, D. A. ^{[1
,4
]}

Campbell, J. E. ^{[1
,4
,5
]}

机构：

[1] Duke Univ, Duke Mol Physiol Inst, Durham, NC 27708 USA

[2] Univ Wisconsin, Dept Med, Div Endocrinol Diabet & Metab, Madison, WI USA

[3] Eli Lilly & Co, Lilly Res Labs, Diabet & Complicat, Indianapolis, IN 46285 USA

[4] Duke Univ, Dept Med, Div Endocrinol, Durham, NC 27708 USA

[5] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 11期

基金：

美国国家卫生研究院;

关键词：

GASTRIC-INHIBITORY POLYPEPTIDE; DEPENDENT INSULINOTROPIC POLYPEPTIDE; GLUCAGON-SECRETION; RECEPTOR; HORMONE; ANTAGONIST; GLP-1; AMIDE;

D O I：

10.1126/sciadv.abf1948

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on beta cells. The GIPR is also expressed in a cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid-stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in beta cells. Moreover, we demonstrate that GIP activity in a cells contributes to insulin secretion by invoking paracrine alpha to beta cell communication. Last, specific loss of GIPR activity in alpha cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in a cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.

引用

页数：10

共 38 条

[1] High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting [J].