Impaired beta-cell regeneration in perinatally malnourished rats: a study with STZ.
We investigated the mechanisms implicated in beta-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 beta-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 beta 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/cm(2), and also through moderately increased beta-cell proliferation. In contrast, beta-cell mass from R-STZ animals poorly regenerated, despite a dramatic increase of beta-cell proliferation, because islet number/cm(2) recovered insufficiently. In conclusion, perinatal malnutrition impairs neogenesis and the capacity of beta-cell regeneration by neogenesis but preserves beta-cell proliferation, which remains the elective choice to increase beta-cell mass. These results provide an explanation for the impaired capacity of malnourished animals to adapt their beta-cell mass during aging or pregnancy, which aggravate glucose tolerance.
Garofano
A
A
INSERM U 457, Hôpital Robert Debré, Paris, France.
Czernichow
P
P
Bréant
B
B
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002452:Cell Count; D002455:Cell Division; D048429:Cell Size; D003921:Diabetes Mellitus, Experimental; D005951:Glucose Tolerance Test; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009748:Nutrition Disorders / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D013311:Streptozocin / Q000633:toxicity
D013311:Streptozocin