Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas)

Guardado Mendoza, Rodolfo; Perego, Carla; Finzi, Giovanna; La Rosa, Stefano; Capella, Carlo; Jimenez-Ceja, Lilia M.; Velloso, Licio A.; Saad, Mario J. A.; Sessa, Fausto; Bertuzzi, Federico; Moretti, Stefania; Dick, Edward J.; Davalli, Alberto M.; Folli, Franco

doi:10.1007/s00125-015-3625-5

Cited by 41Pancreatic function and diabetesDiabetes and associated disordersDiabetes Treatment and Management

Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas)

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Guardado Mendoza, Rodolfo, Perego, Carla, Finzi, Giovanna, La Rosa, Stefano, Capella, Carlo, Jimenez-Ceja, Lilia M., Velloso, Licio A., Saad, Mario J. A. +6 more·2015·Diabetologia

DOI 10.1007/s00125-015-3625-5PMC PMC5603258

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Abstract

Aims/hypothesis The cellular composition of the islet of Langerhans is essential to ensure its physiological function. Morphophysiological islet abnormalities are present in type 2 diabetes but the relationship between fasting plasma glucose (FPG) and islet cell composition, particularly the role of delta cells, is unknown. We explored these questions in pancreases from baboons (Papio hamadryas) with FPG ranging from normal to type 2 diabetic values.Methods We measured the volumes of alpha, beta and delta cells and amyloid in pancreatic islets of 40 baboons (Group 1 [G1]: FPG < 4.44 mmol/l [n = 10]; G2: FPG = 4.44-5.26 mmol/l [n = 9]; G3: FPG = 5.27-6.94 mmol/l [n = 9]; G4: FPG > 6.94 mmol/l [n = 12]) and correlated islet composition with metabolic and hormonal variables. We also performed confocal microscopy including TUNEL, caspase-3, and anti-caspase cleavage product of cytokeratin 18 (M30) immunostaining, electron microscopy, and immuno-electron microscopy with anti-somatostatin antibodies in baboon pancreases.Results Amyloidosis preceded the decrease in beta cell volume. Alpha cell volume increased ∼ 50% in G3 and G4 (p < 0.05), while delta cell volume decreased in these groups by 31% and 39%, respectively (p < 0.05). In G4, glucagon levels were higher, while insulin and HOMA index of beta cell function were lower than in the other groups. Immunostaining of G4 pancreatic sections with TUNEL, caspase-3 and M30 showed apoptosis of beta and delta cells, which was also confirmed by immuno-electron microscopy with anti-somatostatin antibodies.Conclusions/interpretation In diabetic baboons, changes in islet composition correlate with amyloid deposition, with increased alpha cell and decreased beta and delta cell volume and number due to apoptosis. These data argue for an important role of delta cells in type 2 diabetes.

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Delta-cell number and volume are decreased in baboons with impaired fasting glucose by ~41%, due to apoptosis.
“Interestingly, a recent study found that the delta-cell number and volume were decreased in baboons with impaired fasting glucose by ~41%, and this was due to apoptosis.155”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [155]

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Authors: Guardado Mendoza, R., Perego, C., Finzi, G., La Rosa, S., Capella, C., Jimenez-Ceja, L. M., Velloso, L. A., Saad, M. J. A., Sessa, F., Bertuzzi, F., Moretti, S., Dick, E. J., Davalli, A. M., & Folli, F.
Affiliations: University of Milan (IT)
University of Insubria (IT)
Universidade Estadual de Campinas (UNICAMP) (BR)
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
Texas Biomedical Research Institute (US)
IRCCS Ospedale San Raffaele (IT)
Corresponding author: Folli, Franco
ORCID: Perego, Carla
Finzi, Giovanna
Velloso, Licio A.
Sessa, Fausto
Bertuzzi, Federico
Dick, Edward J.
Folli, Franco
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2015-06-07
Volume: 58
Issue: 8
Pages: 1814-1826
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-015-3625-5
PMC: PMC5603258
OpenAlex: W610679515
Cited by: 41
References: 50
Citations by year: 2025: 3 · 2024: 7 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 1
FWCI: 4.03
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
IrInSubria (University of Insubria) (submittedVersion)
Funders: National Institutes of Health (P51OD011133)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080148, NIH RO1 DK080148)
National Center for Research Resources (C06RR015456, M01RR01346, M01RR001346, P51RR013986, C06RR014578)
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: delta cells, somatostatin, type 2 diabetes, pancreatic islets, beta-cell apoptosis, alpha cell hyperplasia, fasting blood glucose, baboons, islet cell composition, caspase-3, cytokeratin 18, glucagon, insulin resistance
MeSH terms: Animals, Blood Glucose, Diabetes Mellitus, Type 2, Female, Insulin Resistance, Islets of Langerhans, Male, Cell Death, Disease Progression, Somatostatin-Secreting Cells, Papio hamadryas, Glucagon-Secreting Cells, Insulin-Secreting Cells, Caspase 3

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Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas)

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