Abstract.
In the Goto-Kakizaki (GK) rat, a genetic model of type II diabetes, there is a restriction of the β-cell mass as early as fetal age, which is maintained reduced in the adult animal. In order to investigate the β-cell growth potential in the adult hyperglycemic GK rat, and to determine whether it differs from non-diabetic Wistar (W) rats, we have performed 90% pancreatectomy (Px) in 8- to 10-week-old male animals. Spontaneous β-cell regeneration and involvement of β-cell replication, β-cell neodifferentiation from ductal precursor, and β-cell apoptosis were evaluated by immunocytochemistry and morphometry at different time points: day 0 (D0), D2, D7, and D14 after Px. In GK rats, deterioration of the diabetic state with severe and chronic hyperglycemia was evident as soon as D2, while in W/Px, normoglycemia to moderate hyperglycemia was observed. In W/Px rats, the total β-cell mass gradually increased on D2, D7, and D14, as compared to non-Px W rats. By contrast, in GK/Px rats, there was only a non-significant tendency to increased total β-cell mass, as compared to related non-Px group. Adult GK rats displayed lower β-cell proliferation rates compared to W. In response to Px, early increase of β-cell proliferation was present in both W/Px and GK/Px rats on D2, but it returned to non-Px values in GK rats on D7 and D14, while in W/Px rats β-cell proliferation was maintained increased as compared to non-Px W rats. The very low apoptotic β-cell frequency on D0, D2, D7, and D14, in both W and GK, either non-Px or Px, did not allow us to conclude that any significant differences exist between the different groups. β-cell neoformation from ducts, and more specifically from foci of regeneration, was found to be less activated in GK/Px rats as compared to W/Px. Together, these results suggest that in the adult hyperglycemic GK rat undergoing Px, β-cells still have the capacity to regenerate, but with a lower efficiency as compared to non-diabetic W rats. This defect in the GK rat is the result of both genetic predisposition contributing to an altered β-cell neogenesis potential already present in the neonatal period, and environmental factors (chronic hyperglycemia) leading to a reduced β-cell proliferative capacity specific to the adult animals.
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Plachot, C., Movassat, J. & Portha, B. Impaired β-cell regeneration after partial pancreatectomy in the adult Goto-Kakizaki rat, a spontaneous model of type II diabetes. Histochem Cell Biol 116, 131–139 (2001). https://doi.org/10.1007/s004180100302
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DOI: https://doi.org/10.1007/s004180100302