Beta-cell proliferation in normal and streptozotocin-treated newborn rats: site, dynamics and capacity

Diabetologia. 1994 Nov;37(11):1088-96. doi: 10.1007/BF00418372.


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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Division
  • DNA / biosynthesis
  • DNA Replication
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Experimental / physiopathology
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Insulin / analysis
  • Islets of Langerhans / cytology
  • Islets of Langerhans / pathology*
  • Islets of Langerhans / physiopathology
  • Pancreatic Ducts / physiology
  • Proinsulin / analysis
  • Protein Precursors / analysis
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Regeneration
  • Streptozocin


  • Insulin
  • Protein Precursors
  • RNA, Messenger
  • Streptozocin
  • preproinsulin
  • DNA
  • Proinsulin