Activation of the GLP-1 Receptor Signalling Pathway: A Relevant Strategy to Repair a Deficient Beta-Cell Mass
Figure 1
GLP-1 or Exendin-4 (Ex-4) activates beta-cells regeneration in vivo. The aim was to investigate in the rat model of neonatal beta-cell regeneration (nSTZ model), the capacity of in vivo treatments with GLP-1 or Ex-4 to promote beta-cell regeneration. To this end, nSTZ rats from the Wistar strain (W) were submitted to GLP-1 or Ex-4 administration from postnatal day 2 to day 6 only, and their beta-cell masses were tested on day 7 (a) and (b). In the nSTZ/GLP-1 and nSTZ/Ex-4 groups, total beta-cell masses per pancreas were both significantly increased (***) as compared with values in untreated nSTZ rats, representing, respectively, 51% and 71% of the control Wistar beta-cell mass, while nSTZ beta-cell mass represented only 21% of the control Wistar value. Beta-cell BrdU labeling index (c) in the untreated nSTZ rats was found to be significantly increased () as compared with Wistar group. In the nSTZ/GLP-1 and nSTZ/Ex-4 groups, it was similarly increased. A representative figure is given with double immunostaining for BrdU and insulin in 7-day-old nSTZ rats (magnification ×1000). To estimate activation of neogenesis (d) and (e), the number of single beta-cells incorporated into the duct epithelium and the number of beta-cell clusters budding from ducts were quantified. The number of isolated beta-cell within pancreatic tissue of nSTZ rats represented 185% of Wistar value and the number of beta-cell buds in pancreatic tissue in nSTZ rats represented 106% of Wistar value. These two parameters were strongly increased in nSTZ/GLP-1 and nSTZ/Ex-4 rats as compared to untreated nSTZ rats (***). A representative figure is given with indirect immunoperoxydase staining for insulin in 7 day-old nSTZ/GLP-1 rats (magnification ×1000). Adapted from Tourrel et al. [83].
