Differential expression of glucagon-like peptide-2 (GLP-2) is involved in pancreatic islet cell adaptations to stress and beta-cell survival

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Abstract

Recent studies have confirmed that locally released proglucagon derived gene products, other than glucagon, have a major influence on pancreatic endocrine function. We assessed the impact of glucagon-like peptide-2 (GLP-2) on beta-cell secretory function, proliferation and apoptosis, as well as glucose tolerance, feeding behaviour and islet adaptions to chemically-induced insulin deficiency and resistance. The GLP-2 receptor was evidenced on cultured rodent and human beta-cells, rodent alpha-cells and isolated mouse islets. GLP-2 had no effect on insulin secretion from beta-cells, or isolated mouse islets. In vivo, GLP-2 administration significantly (P <0.05 to P <0.01) decreased food intake in mice. Conversely, GLP-2 had no discernible effects on glucose disposal or insulin secretion. As expected, streptozotocin treatment decreased and hydrocortisone increased beta-cell mass in mice. GLP-2 was visualised in mouse islets and intestinal L-cells. Islet GLP-2 co-localisation with glucagon was significantly decreased (P <0.01) by both streptozotocin and hydrocortisone. In contrast, both interventions increased (P <0.05) co-localisation of GLP-2 with somatostatin. Interestingly, GLP-2 positive cells were reduced (P <0.05) in the intestines of streptozotocin, but not hydrocortisone, treated mice. Further in vitro investigations revealed that GLP-2 protected rodent and human 1.1B4 beta-cells against streptozotocin induced DNA damage. Furthermore, GLP-2 augmented (P <0.05) BRIN BD11 beta-cell proliferation, but was less efficacious in 1.1B4 cells. These data highlight the involvement of GLP-2 receptor signalling in the adaptations to pancreatic islet cell stress.
Original languageEnglish
Pages (from-to)68-75
JournalPeptides
Volume95
Early online date23 Jul 2017
DOIs
Publication statusE-pub ahead of print - 23 Jul 2017

Keywords

  • Beta-cell
  • alpha-cell
  • islets
  • proglucagon
  • GLP-2
  • GLP-2 receptor
  • insulin secretion
  • diabetes
  • proliferation
  • apoptosis

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