The insulinotrophic effect of insulin-like peptide 5 in vitro and in vivo

Biochem J. 2015 Mar 15;466(3):467-73. doi: 10.1042/BJ20141113.


Insulin-like peptide 5 (INSL5), a member of the insulin/relaxin superfamily, can activate the G-protein-coupled receptor relaxin/insulin-like family peptide receptor 4 (RXFP4), but its precise biological functions are largely unknown. Recent studies suggest that INSL5/RXFP4 is involved in the control of food intake and glucose homoeostasis. We report in the present study that RXFP4 is present in the mouse insulinoma cell line MIN6 and INSL5 augments glucose-stimulated insulin secretion (GSIS) both in vitro and in vivo. RXFP4 is also expressed in the mouse intestinal L-cell line GLUTag and INSL5 is capable of potentiating glucose-dependent glucagon-like peptide-1 (GLP-1) secretion in GLUTag cells. We propose that the insulinotrophic effect of INSL5 is probably mediated through stimulation of insulin/GLP-1 secretion and the INSL5/RXFP4 system may be a potential therapeutic target for Type 2 diabetes.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Glucagon-Like Peptide 1 / blood
  • HEK293 Cells
  • Humans
  • Insulin / blood
  • Insulinoma / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pancreatic Neoplasms / metabolism*
  • Peptide Hormones / pharmacology*


  • Blood Glucose
  • Insl5 protein, mouse
  • Insulin
  • Peptide Hormones
  • Glucagon-Like Peptide 1