Protein restriction during pregnancy impairs intra-islet GLP-1 and the expansion of β-cell mass

Mol Cell Endocrinol. 2020 Dec 1:518:110977. doi: 10.1016/j.mce.2020.110977. Epub 2020 Aug 11.

Abstract

We evaluated whether protein restriction during pregnancy alters the morphometry of pancreatic islets, the intra-islet glucagon-like peptide-1 (GLP-1) production, and the anti-apoptotic signalling pathway modulated by GLP-1. Control non-pregnant (CNP) and control pregnant (CP) rats were fed a 17% protein diet, and low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) groups were fed a 6% protein diet. The masses of islets and β-cells were similar in the LPNP group and the CNP group but were higher in the CP group than in the CNP group and were equal in the LPP group and the LPNP group. Both variables were lower in the LPP group than in the CP group. Prohormone convertase 2 and GLP-1 fluorescence in α-cells was lower in the low-protein groups than in the control groups. The least PC2/glucagon colocalization was observed in the LPP group, and the most was observed in the CP group. There was less prohormone convertase 1/3/glucagon colocalization in the LPP group than in the CP group. GLP-1/glucagon colocalization was similar in the LPP, CP and CNP groups, which showed less GLP-1/glucagon colocalization than the LPNP group. The mRNA Pka, Creb and Pdx-1 contents were higher in islets from pregnant rats than in islets from non-pregnant rats. Protein restriction during pregnancy impaired the mass of β-cells and the intra-islet GLP-1 production but did not interfere with the transcription of genes of the anti-apoptotic signalling pathway modulated by GLP-1.

Keywords: Apoptosis; Intra-islet GLP-1 production; Islet morphometry; Pregnancy; Prohormone convertases; Protein restriction; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, Protein-Restricted / adverse effects*
  • Down-Regulation
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks / drug effects
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Pregnancy
  • Proprotein Convertase 2 / metabolism
  • Rats

Substances

  • Glucagon-Like Peptide 1
  • Glucagon
  • Proprotein Convertase 2