Impaired β‐cell regeneration in perinatally malnourished rats: a study with STZ

A Garofano, P Czernichow, B BrÉant - The FASEB Journal, 2000 - Wiley Online Library
A Garofano, P Czernichow, B BrÉant
The FASEB Journal, 2000Wiley Online Library
We investigated the mechanisms implicated in β‐cell mass reduction observed during late
fetal and early postnatal malnutrition in the rat. Beta‐cell regeneration, including proliferation
and neogenesis, was studied after neonatal β‐cell destruction by streptozotocin (STZ). STZ
was injected at birth and maternal food restriction was continued until weaning. Beta‐cell
mass, proliferation, and islet number were quantified by morphometrical measurements on
pancreatic sections in STZ‐injected normal (C‐STZ) and malnourished (R‐STZ) rats, with …
Abstract
We investigated the mechanisms implicated in β‐cell mass reduction observed during late fetal and early postnatal malnutrition in the rat. Beta‐cell regeneration, including proliferation and neogenesis, was studied after neonatal β‐cell destruction by streptozotocin (STZ). STZ was injected at birth and maternal food restriction was continued until weaning. Beta‐cell mass, proliferation, and islet number were quantified by morphometrical measurements on pancreatic sections in STZ‐injected normal (C‐STZ) and malnourished (R‐STZ) rats, with noninjected C and R rats as controls. At day 4, only 20% of the β cell‐mass remained in C‐STZ rats. It regenerated to 50% that of noninjected controls, mainly through active neogenesis, as shown by the entire recovery of islet number/cm2, and also through moderately increased β‐cell proliferation. In contrast, β ‐cell mass from R‐STZ animals poorly regenerated, despite a dramatic increase of β ‐cell proliferation, because islet number/cm2 recovered insufficiently. In conclusion, perinatal malnutrition impairs neogenesis and the capacity of β ‐cell regeneration by neogenesis but preserves β‐cell proliferation, which remains the elective choice to increase β ‐cell mass. These results provide an explanation for the impaired capacity of malnourished animals to adapt their β ‐cell mass during aging or pregnancy, which aggravate glucose tolerance.—Garofano, A., Czernichow, P., and Breant, B. Impaired β‐cell regeneration in perinatally malnourished rats: a study with STZ. FASEB J. 14, 2611–2617 (2000)
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