Skip to main content

β-Cell Inactivation of Gpr119 Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation.

Publication ,  Journal Article
Panaro, BL; Flock, GB; Campbell, JE; Beaudry, JL; Cao, X; Drucker, DJ
Published in: Diabetes
June 2017

GPR119 was originally identified as an orphan β-cell receptor; however, subsequent studies demonstrated that GPR119 also regulates β-cell function indirectly through incretin hormone secretion. We assessed the importance of GPR119 for β-cell function in Gpr119-/- mice and in newly generated Gpr119βcell-/- mice. Gpr119-/- mice displayed normal body weight and glucose tolerance on a regular chow (RC) diet. After high-fat feeding, Gpr119-/- mice exhibited reduced fat mass, decreased levels of circulating adipokines, improved insulin sensitivity, and better glucose tolerance. Unexpectedly, oral and intraperitoneal glucose tolerance and the insulin response to glycemic challenge were not perturbed in Gpr119βcell-/- mice on RC and high-fat diets. Moreover, islets from Gpr119-/- and Gpr119βcell-/- mice exhibited normal insulin responses to glucose and β-cell secretagogues. Furthermore, the selective GPR119 agonist AR231453 failed to directly enhance insulin secretion from perifused islets. In contrast, AR231453 increased plasma glucagon-like peptide 1 (GLP-1) and insulin levels and improved glucose tolerance in wild-type and Gpr119βcell-/- mice. These findings demonstrate that β-cell GPR119 expression is dispensable for the physiological control of insulin secretion and the pharmacological response to GPR119 agonism, findings that may inform the lack of robust efficacy in clinical programs assessing GPR119 agonists for the therapy of type 2 diabetes.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

June 2017

Volume

66

Issue

6

Start / End Page

1626 / 1635

Location

United States

Related Subject Headings

  • Receptors, G-Protein-Coupled
  • Pyrimidines
  • Oxadiazoles
  • Mice, Knockout
  • Male
  • Insulin-Secreting Cells
  • Insulin Secretion
  • Insulin Resistance
  • Insulin
  • Incretins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Panaro, B. L., Flock, G. B., Campbell, J. E., Beaudry, J. L., Cao, X., & Drucker, D. J. (2017). β-Cell Inactivation of Gpr119 Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation. Diabetes, 66(6), 1626–1635. https://doi.org/10.2337/db17-0017
Panaro, Brandon L., Grace B. Flock, Jonathan E. Campbell, Jacqueline L. Beaudry, Xiemin Cao, and Daniel J. Drucker. “β-Cell Inactivation of Gpr119 Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation.Diabetes 66, no. 6 (June 2017): 1626–35. https://doi.org/10.2337/db17-0017.
Panaro BL, Flock GB, Campbell JE, Beaudry JL, Cao X, Drucker DJ. β-Cell Inactivation of Gpr119 Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation. Diabetes. 2017 Jun;66(6):1626–35.
Panaro, Brandon L., et al. “β-Cell Inactivation of Gpr119 Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation.Diabetes, vol. 66, no. 6, June 2017, pp. 1626–35. Pubmed, doi:10.2337/db17-0017.
Panaro BL, Flock GB, Campbell JE, Beaudry JL, Cao X, Drucker DJ. β-Cell Inactivation of Gpr119 Unmasks Incretin Dependence of GPR119-Mediated Glucoregulation. Diabetes. 2017 Jun;66(6):1626–1635.

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

June 2017

Volume

66

Issue

6

Start / End Page

1626 / 1635

Location

United States

Related Subject Headings

  • Receptors, G-Protein-Coupled
  • Pyrimidines
  • Oxadiazoles
  • Mice, Knockout
  • Male
  • Insulin-Secreting Cells
  • Insulin Secretion
  • Insulin Resistance
  • Insulin
  • Incretins