Beta-cell proliferation in normal and streptozotocin-treated newborn rats: site, dynamics and capacity.
Regeneration of neonatal beta cells after streptozotocin (STZ)-induced destruction may be due to either replication from pre-existing intra-islet beta cells or extra-islet precursor cells. To further investigate this issue, beta-cell growth was analysed in normal and streptozotocin-treated newborn rats (100 micrograms/g body weight) at several time points during the first 20 days of life. Beta cells were identified by insulin immunostaining, non-isotopic in situ hybridization for rat preproinsulin mRNA, and electron microscopy. Their proliferative activity was recorded by bromodeoxyuridine-pulse labelling. Beta-cell size and total volume were determined by computerized morphometry. In normal rats, there was a threefold increase in total beta-cell volume during the first 5 days of life, with no further expansion till day 20. The bromodeoxyuridine labelling index of the intra-islet beta cells was smaller than that of the extra-islet beta cells (2-3% vs 15-20%). Comparison of the cell birth rate, calculated from the beta-cell labelling index, with the observed increase in beta-cell volume suggested that in normal neonatal rats proliferation of the intra-islet beta-cell population could account for only 10% of the observed expansion. Administration of streptozotocin at birth resulted in more than 90% reduction of the total beta-cell volume at day 2 which then increased to 39% of the normal value by day 20. During this period of partial regeneration, which restored normoglycaemia, the labelling index of intra-islet beta cells was higher than in normal rats (9% vs 2%, p < 0.001), whereas no change was seen in the extra-islet beta-cell labelling index.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
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RN
Department of Experimental Pathology, Free University of Brussels, Belgium.
Bouwens
L
L
Klöppel
G
G
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology / Q000473:pathology* / Q000503:physiopathology; D010183:Pancreatic Ducts / Q000502:physiology; D011384:Proinsulin / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D013311:Streptozocin
D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; D013311:Streptozocin; C013737:preproinsulin; D004247:DNA; D011384:Proinsulin