Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes

Yoshifumi Saisho, Erica Manesso, Alexandra E. Butler, Ryan Galasso, Kylie Kavanagh, Mickey Flynn, Li Zhang, Paige Clark, Tatyana Gurlo, Gianna M. Toffolo, Claudio Cobelli, Janice D. Wagner, Peter C. Butler

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

OBJECTIVE - β-Cell turnover and its potential to permit β-cell regeneration in adult primates are unknown. Our aims were 1) to measure β-cell turnover in adult nonhuman primates; 2) to establish the relative contribution of β-cell replication and formation of new β-cells from other precursors (defined thus as β-cell neogenesis); and 3) to establish whether there is an adaptive increase in β-cell formation (attempted regeneration) in streptozotocin (STZ)-induced diabetes in adult nonhuman primates. RESEARCH DESIGN AND METHODS - Adult (aged 7 years) vervet monkeys were administered STZ (45-55 mg/kg, n = 7) or saline (n = 9). Pancreas was obtained from each animal twice, first by open surgical biopsy and then by euthanasia. b-Cell turnover was evaluated by applying a mathematic model to measured replication and apoptosis rates. RESULTS - β-Cell turnover is present in adult nonhuman primates (3.3 ± 0.9 mg/month), mostly (;80%) derived from β-cell neogenesis. β-Cell formation was minimal in STZ-induced diabetes. Despite marked hyperglycemia, β-cell apoptosis was not increased in monkeys administered STZ. CONCLUSIONS - There is ongoing β-cell turnover in adult nonhuman primates that cannot be accounted for by β-cell replication. There is no evidence of β-cell regeneration in monkeys administered STZ. Hyperglycemia does not induce b-cell apoptosis in nonhuman primates in vivo.

Original languageEnglish
Pages (from-to)848-856
Number of pages9
JournalDiabetes
Volume60
Issue number3
DOIs
Publication statusPublished - 2011 Mar
Externally publishedYes

Fingerprint

Experimental Diabetes Mellitus
Primates
Streptozocin
Regeneration
Apoptosis
Hyperglycemia
Haplorhini
Cercopithecus aethiops
Euthanasia
Mathematics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Saisho, Y., Manesso, E., Butler, A. E., Galasso, R., Kavanagh, K., Flynn, M., ... Butler, P. C. (2011). Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes. Diabetes, 60(3), 848-856. https://doi.org/10.2337/db09-1368

Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes. / Saisho, Yoshifumi; Manesso, Erica; Butler, Alexandra E.; Galasso, Ryan; Kavanagh, Kylie; Flynn, Mickey; Zhang, Li; Clark, Paige; Gurlo, Tatyana; Toffolo, Gianna M.; Cobelli, Claudio; Wagner, Janice D.; Butler, Peter C.

In: Diabetes, Vol. 60, No. 3, 03.2011, p. 848-856.

Research output: Contribution to journalArticle

Saisho, Y, Manesso, E, Butler, AE, Galasso, R, Kavanagh, K, Flynn, M, Zhang, L, Clark, P, Gurlo, T, Toffolo, GM, Cobelli, C, Wagner, JD & Butler, PC 2011, 'Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes', Diabetes, vol. 60, no. 3, pp. 848-856. https://doi.org/10.2337/db09-1368
Saisho, Yoshifumi ; Manesso, Erica ; Butler, Alexandra E. ; Galasso, Ryan ; Kavanagh, Kylie ; Flynn, Mickey ; Zhang, Li ; Clark, Paige ; Gurlo, Tatyana ; Toffolo, Gianna M. ; Cobelli, Claudio ; Wagner, Janice D. ; Butler, Peter C. / Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes. In: Diabetes. 2011 ; Vol. 60, No. 3. pp. 848-856.
@article{a886f692e05a4183a77ba56d0f6a8dec,
title = "Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes",
abstract = "OBJECTIVE - β-Cell turnover and its potential to permit β-cell regeneration in adult primates are unknown. Our aims were 1) to measure β-cell turnover in adult nonhuman primates; 2) to establish the relative contribution of β-cell replication and formation of new β-cells from other precursors (defined thus as β-cell neogenesis); and 3) to establish whether there is an adaptive increase in β-cell formation (attempted regeneration) in streptozotocin (STZ)-induced diabetes in adult nonhuman primates. RESEARCH DESIGN AND METHODS - Adult (aged 7 years) vervet monkeys were administered STZ (45-55 mg/kg, n = 7) or saline (n = 9). Pancreas was obtained from each animal twice, first by open surgical biopsy and then by euthanasia. b-Cell turnover was evaluated by applying a mathematic model to measured replication and apoptosis rates. RESULTS - β-Cell turnover is present in adult nonhuman primates (3.3 ± 0.9 mg/month), mostly (;80{\%}) derived from β-cell neogenesis. β-Cell formation was minimal in STZ-induced diabetes. Despite marked hyperglycemia, β-cell apoptosis was not increased in monkeys administered STZ. CONCLUSIONS - There is ongoing β-cell turnover in adult nonhuman primates that cannot be accounted for by β-cell replication. There is no evidence of β-cell regeneration in monkeys administered STZ. Hyperglycemia does not induce b-cell apoptosis in nonhuman primates in vivo.",
author = "Yoshifumi Saisho and Erica Manesso and Butler, {Alexandra E.} and Ryan Galasso and Kylie Kavanagh and Mickey Flynn and Li Zhang and Paige Clark and Tatyana Gurlo and Toffolo, {Gianna M.} and Claudio Cobelli and Wagner, {Janice D.} and Butler, {Peter C.}",
year = "2011",
month = "3",
doi = "10.2337/db09-1368",
language = "English",
volume = "60",
pages = "848--856",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "3",

}

TY - JOUR

T1 - Ongoing β-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes

AU - Saisho, Yoshifumi

AU - Manesso, Erica

AU - Butler, Alexandra E.

AU - Galasso, Ryan

AU - Kavanagh, Kylie

AU - Flynn, Mickey

AU - Zhang, Li

AU - Clark, Paige

AU - Gurlo, Tatyana

AU - Toffolo, Gianna M.

AU - Cobelli, Claudio

AU - Wagner, Janice D.

AU - Butler, Peter C.

PY - 2011/3

Y1 - 2011/3

N2 - OBJECTIVE - β-Cell turnover and its potential to permit β-cell regeneration in adult primates are unknown. Our aims were 1) to measure β-cell turnover in adult nonhuman primates; 2) to establish the relative contribution of β-cell replication and formation of new β-cells from other precursors (defined thus as β-cell neogenesis); and 3) to establish whether there is an adaptive increase in β-cell formation (attempted regeneration) in streptozotocin (STZ)-induced diabetes in adult nonhuman primates. RESEARCH DESIGN AND METHODS - Adult (aged 7 years) vervet monkeys were administered STZ (45-55 mg/kg, n = 7) or saline (n = 9). Pancreas was obtained from each animal twice, first by open surgical biopsy and then by euthanasia. b-Cell turnover was evaluated by applying a mathematic model to measured replication and apoptosis rates. RESULTS - β-Cell turnover is present in adult nonhuman primates (3.3 ± 0.9 mg/month), mostly (;80%) derived from β-cell neogenesis. β-Cell formation was minimal in STZ-induced diabetes. Despite marked hyperglycemia, β-cell apoptosis was not increased in monkeys administered STZ. CONCLUSIONS - There is ongoing β-cell turnover in adult nonhuman primates that cannot be accounted for by β-cell replication. There is no evidence of β-cell regeneration in monkeys administered STZ. Hyperglycemia does not induce b-cell apoptosis in nonhuman primates in vivo.

AB - OBJECTIVE - β-Cell turnover and its potential to permit β-cell regeneration in adult primates are unknown. Our aims were 1) to measure β-cell turnover in adult nonhuman primates; 2) to establish the relative contribution of β-cell replication and formation of new β-cells from other precursors (defined thus as β-cell neogenesis); and 3) to establish whether there is an adaptive increase in β-cell formation (attempted regeneration) in streptozotocin (STZ)-induced diabetes in adult nonhuman primates. RESEARCH DESIGN AND METHODS - Adult (aged 7 years) vervet monkeys were administered STZ (45-55 mg/kg, n = 7) or saline (n = 9). Pancreas was obtained from each animal twice, first by open surgical biopsy and then by euthanasia. b-Cell turnover was evaluated by applying a mathematic model to measured replication and apoptosis rates. RESULTS - β-Cell turnover is present in adult nonhuman primates (3.3 ± 0.9 mg/month), mostly (;80%) derived from β-cell neogenesis. β-Cell formation was minimal in STZ-induced diabetes. Despite marked hyperglycemia, β-cell apoptosis was not increased in monkeys administered STZ. CONCLUSIONS - There is ongoing β-cell turnover in adult nonhuman primates that cannot be accounted for by β-cell replication. There is no evidence of β-cell regeneration in monkeys administered STZ. Hyperglycemia does not induce b-cell apoptosis in nonhuman primates in vivo.

UR - http://www.scopus.com/inward/record.url?scp=79952369836&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952369836&partnerID=8YFLogxK

U2 - 10.2337/db09-1368

DO - 10.2337/db09-1368

M3 - Article

VL - 60

SP - 848

EP - 856

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -