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BERNARD PORTHA AN. R. ACAD. NAC. FARM.

FIGURE 5. GLP-1 or Exendin-4 treatment promotes beta-cell proliferation in
GK rats during the pre-diabetic stage and thereby prevents the pathological
progression of the T2D when animals become adults. Left panel: Evolution of

post-absorptive basal plasma glucose levels of W, GK, GK/GLP-1 and GK/Ex-4
from 7 days to 2 months of age. Values are expressed as mean ± SEM. In each
group, 10 to 15 animals were studied. Right panel: Total pancreatic beta-cell mass

quantification in 60-day-old W, GK, GK/GLP-1 and GK/Ex-4 rats. Values are
expressed as mean ± SEM for 4 observations in each group. ** p<0.01; * p<0.05

compared with untreated GK rat.

endocrine pancreas (decreased beta-cell neogenesis) which is
transmitted to the next generation; and (iii) secondary (acquired)
loss of beta-cell differentiation due to chronic exposure to
hyperglycaemia (glucotoxicity). An important message is that the
«heritable» determinants of T2D are not simply dependant of genetic
factors, but probably involve transgenerational epigenetic responses.

ACKNOWLEDGMENTS

This review is a modified version of the conference I presented
on April 19, 2007, with the occasion of becoming Académico
Correspondiente extranjero of the Real Academia Nacional de
Farmacia. I thank Dr. Ana-María Pascual-Leone for spanish version

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