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Cited by 324Pancreatic function and diabetesDiabetes and associated disordersEndoplasmic Reticulum Stress and Disease

Responses of Neonatal Rat Islets to Streptozotocin: Limited B-Cell Regeneration and Hyperglycemia

Bonner-Weir, S, Trent, D F, Honey, R N, Weir, G C·1981·Diabetes
DOI 10.2337/diab.30.1.64
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Abstract

Streptozotocin (SZ) was given to 2-day-old neonatal rats, and, during their subsequent development, the interrelationships between plasma glucose, plasma insulin, pancreatic islet morphology, and hormone content were examined. At 4 days of age, a peak of hyperglycemia was observed (SZ, 349 ± 8 mg/dl versus control (C), 127 ± 2) that was associated with a marked reduction of B-cell numbers (SZ, 26.5 ± 2.6% B-cell per islet versus C, 72.8 ± 0.8%). By 10 days of age the SZ animals became normoglycemic with partial recovery of the B-cell number (SZ, 39.6 ± 2.1% versus C, 64.0 ± 2.6%). By 6 weeks hyperglycemia returned (SZ, 345 ± 5.2 mg/dl versus C, 171 ± 6.2) with B-cell number of the SZ being 72% of the C (SZ, 48.8 ± 2.4% versus C, 67.5 ± 1.5%). This hyperglycemia and reduced B-cell number persisted to at least 13 wk age. Despite a marked reduction of pancreatic insulin content observed during development, there was little effect upon glucagon or somatostatin content. At 6 wk of age, the plasma insulin concentration was only 30% of C, which suggests an insulin secretory defect beyond that which could be accounted for by the modest B-cell reduction. The present study indicates that even though active regeneration of B-celle occurred after early injury, the capacity for ultimate normalization was limited. The resultant moderate reduction in B-cell number may be associated with a functional defect in glucose-stimulated insulin secretion.

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  • A single injection of STZ leads to loss of approximately 50% of β-cells.

    “we adapted a standard regeneration model that uses a single injection of STZ to lead to a loss of ∼50% of the β-cells (31).”

    From Age-Dependent Decline in β-Cell Proliferation Restricts the Capacity of β-Cell Regeneration in Mice (2009) · cites this paper as [31]

  • An increase in β-cell proliferation is observed 7 days after STZ injection and correlates with regeneration of β-cell mass.

    “We used this model for two reasons:1) an increase in β-cell proliferation is observed 7 days after STZ injection that correlates with regeneration of β-cell mass, and 2) the residual β-cell mass is sufficient to maintain blood glucose levels, thus potentially minimizing the role of hyperglycemia in β-cell proliferation and apoptosis.”

    From Age-Dependent Decline in β-Cell Proliferation Restricts the Capacity of β-Cell Regeneration in Mice (2009) · cites this paper as [31]

  • The residual β-cell mass after STZ is sufficient to maintain blood glucose levels, minimizing the role of hyperglycemia in β-cell proliferation and apoptosis.

    “We used this model for two reasons:1) an increase in β-cell proliferation is observed 7 days after STZ injection that correlates with regeneration of β-cell mass, and 2) the residual β-cell mass is sufficient to maintain blood glucose levels, thus potentially minimizing the role of hyperglycemia in β-cell proliferation and apoptosis.”

    From Age-Dependent Decline in β-Cell Proliferation Restricts the Capacity of β-Cell Regeneration in Mice (2009) · cites this paper as [31]

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Authors
Bonner-Weir, S., Trent, D. F., Honey, R. N., & Weir, G. C.
Affiliations
  • Division of Endocrinology, Department of Medicine, Medical College of Virginia Richmond, Virginia 23298
  • Virginia Commonwealth University Medical Center (US)
ORCID
Weir, G C
Venue
Diabetes
Publisher
American Diabetes Association
Published
1981-01-01
Volume
30
Issue
1
Pages
64-69
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.30.1.64
OpenAlex
W2157604930
Cited by
324
References
0
Citations by year
2026: 4 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 11 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 8 · 2013: 17 · 2012: 14
FWCI
5.46
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
streptozotocin, neonatal rats, pancreatic islets, beta cell regeneration, hyperglycemia, insulin secretion defect, glucagon, somatostatin, islet development, beta-cell injury
MeSH terms
Aging, Animals, Animals, Newborn, Blood Glucose, Body Weight, Eating, Female, Glucagon, Hyperglycemia, Insulin, Islets of Langerhans, Male, Regeneration, Sex Factors, Somatostatin, Streptozocin, Rats

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