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

FIGURE 3. Schematic presentation of the defective early pancreatic
development in the GK/Par rat. Pancreatic cell proliferation and apoptosis and

were estimated at embryonic ages E13.5 and E18.5. Comparison of the dorsal
pancreatic buds in GK and Wistar (W) rats indicates that the differentiation of the

early endocrine cells which appear between E12-E14 is preserved in GK, the
number of insulin- or glucagon-expressing cells being similar to Wistar pancreases.
Analysis of cell proliferation and apoptosis revealed no differences between Wistar

and GK pancreases at this stage. By contrast at E18.5 onward, the number of
beta-cells differentiating from the ductal network is reduced by 74% in the GK rat.
The apoptotic cells in the E18.5 GK pancreas are not endocrine cells since we did

not detect TUNEL-positive cells expressing insulin or glucagon. Moreover these
undifferentiated pancreatic cells exhibit a decreased replicative activity. The

morphological analysis of the sections suggested that the apoptotic cells in the GK
pancreas are ductal cells. IGF-2 protein expression was decreased by 27% and

58% on E13.5 and E18.5 respectively, in GK pancreatic rudiments as compared to
W controls. IGF-1R protein expression was decreased by 42% and 34% on E13.5

and E18.5 respectively in GK pancreatic rudiment as compared to W controls.
Therefore, the defective IGF2 and IGF1-R protein expression within the GK

pancreatic rudiment (E 13.5) precedes the beta-cell mass anomaly. ? represents an
increase, ? represents a decrease, and = means no change.

approach, we have shown that the regeneration of the beta-cell mass
was impaired in streptozotocin-treated newborn GK rats. Because the
index of beta-cell proliferation in the streptozotocin-treated GK and
Wistar neonates was identical, it was concluded that the impaired
beta-cell regeneration of the GK pancreas results from defective
neogenesis (18).

Third, similar conclusions were drawn from duct-cell remodelling
and beta-cell regeneration investigations after partial pancreatectomy
in the adult GK rat (20).

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