Details

Autor(en) / Beteiligte

• Kirk, Rikke K.
• Pyke, Charles
• von Herrath, Matthias G.
• Hasselby, Jane P.
• Pedersen, Lars
• Mortensen, Pia G.
• Knudsen, Lotte B.
• Coppieters, Ken

Titel

Immunohistochemical assessment of glucagon‐like peptide 1 receptor (GLP‐1R) expression in the pancreas of patients with type 2 diabetes

Ist Teil von

• Diabetes, obesity & metabolism, 2017-05, Vol.19 (5), p.705-712

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2017

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Aims Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose‐dependent manner. Incretin‐based therapies, consisting of GLP‐1 receptor (GLP‐1R) agonists and dipeptidyl peptidase‐4 (DPP‐4) inhibitors, are used for the treatment of type 2 diabetes (T2D). Immunohistochemical studies for GLP‐1R expression have been hampered previously by the use of unspecific polyclonal antibodies. This study aimed to assess the expression levels of GLP‐1R in a set of T2D donor samples obtained via nPOD. Methods This study used a new monoclonal antibody to assess GLP‐1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP‐4 inhibitor and 1 with a history of GLP‐1R agonist treatment. A software‐based automated image analysis algorithm was used for quantitating intensities and area fractions of GLP‐1R positive compartments. Results The highest intensity GLP‐1R immunostaining was seen in beta‐cells in islets (average signal intensity, 76.1 [±8.1]). GLP‐1R/insulin double‐labelled single cells or small clusters of cells were also frequently located within or in close vicinity of ductal epithelium in all samples and with the same GLP‐1R immunostaining intensity as found in beta‐cells in islets. In the exocrine pancreas a large proportion of acinar cells expressed GLP‐1R with a 3‐fold lower intensity of immunoreactivity as compared to beta‐cells (average signal intensity 25.5 [±3,3]). Our studies did not unequivocally demonstrate GLP‐1R immunoreactivity on normal‐appearing ductal epithelium. Pancreatic intraepithelial neoplasia (PanINs; a form of non‐invasive pancreatic ductular neoplasia) was seen in most samples, and a minority of these expressed low levels of GLP‐1R. Conclusion These data confirm the ubiquity of early stage PanIN lesions in patients with T2D and do not support the hypothesis that incretin‐based therapies are associated with progression towards the more advanced stage PanIN lesions.