Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates

R. Guardado-Mendoza, L. Jimenez-Ceja, A. Majluf-Cruz, S. Kamath, T. V. Fiorentino, F. Casiraghi, A. O C Velazquez, Ralph A Defronzo, E. Dick, A. Davalli, F. Folli

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Obesity is associated with high insulin and glucagon plasma levels. Enhanced β-cell function and β-cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons. Methods: Pancreatic β-and α-cell volumes were measured in 51 normoglycemic baboons divided into six groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters. Results: Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater increase in RIαV. Baboons' body weights correlated with serum levels of interleukin-6 and tumor necrosis factor-α soluble receptors, demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β-and α-cell viability and replication. Conclusion: In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV), whereas have minimal effects on the β cells. This study suggests that an increase in the α-cell mass may precede the loss of β cells and the transition to overt hyperglycemia and diabetes.

Original languageEnglish (US)
Pages (from-to)1071-1078
Number of pages8
JournalInternational Journal of Obesity
Volume37
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

Cell Size
Primates
Obesity
Islets of Langerhans
Papio
Insulin Resistance
Insulin
Tumor Necrosis Factor Receptors
Glucagon
Hyperglycemia
Pancreas
Interleukin-6
Cell Survival
Body Weight
Cytokines
Serum

Keywords

  • a-cell volume
  • b-cell volume
  • insulin resistance
  • obesity duration
  • obesity severity
  • pancreatic islet remodeling

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Guardado-Mendoza, R., Jimenez-Ceja, L., Majluf-Cruz, A., Kamath, S., Fiorentino, T. V., Casiraghi, F., ... Folli, F. (2013). Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates. International Journal of Obesity, 37(8), 1071-1078. https://doi.org/10.1038/ijo.2012.205

Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates. / Guardado-Mendoza, R.; Jimenez-Ceja, L.; Majluf-Cruz, A.; Kamath, S.; Fiorentino, T. V.; Casiraghi, F.; Velazquez, A. O C; Defronzo, Ralph A; Dick, E.; Davalli, A.; Folli, F.

In: International Journal of Obesity, Vol. 37, No. 8, 08.2013, p. 1071-1078.

Research output: Contribution to journalArticle

Guardado-Mendoza, R, Jimenez-Ceja, L, Majluf-Cruz, A, Kamath, S, Fiorentino, TV, Casiraghi, F, Velazquez, AOC, Defronzo, RA, Dick, E, Davalli, A & Folli, F 2013, 'Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates', International Journal of Obesity, vol. 37, no. 8, pp. 1071-1078. https://doi.org/10.1038/ijo.2012.205
Guardado-Mendoza R, Jimenez-Ceja L, Majluf-Cruz A, Kamath S, Fiorentino TV, Casiraghi F et al. Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates. International Journal of Obesity. 2013 Aug;37(8):1071-1078. https://doi.org/10.1038/ijo.2012.205
Guardado-Mendoza, R. ; Jimenez-Ceja, L. ; Majluf-Cruz, A. ; Kamath, S. ; Fiorentino, T. V. ; Casiraghi, F. ; Velazquez, A. O C ; Defronzo, Ralph A ; Dick, E. ; Davalli, A. ; Folli, F. / Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates. In: International Journal of Obesity. 2013 ; Vol. 37, No. 8. pp. 1071-1078.
@article{70bc7a6ad91e4d8f94694c48ca128e3b,
title = "Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates",
abstract = "Objective: Obesity is associated with high insulin and glucagon plasma levels. Enhanced β-cell function and β-cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons. Methods: Pancreatic β-and α-cell volumes were measured in 51 normoglycemic baboons divided into six groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters. Results: Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater increase in RIαV. Baboons' body weights correlated with serum levels of interleukin-6 and tumor necrosis factor-α soluble receptors, demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β-and α-cell viability and replication. Conclusion: In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV), whereas have minimal effects on the β cells. This study suggests that an increase in the α-cell mass may precede the loss of β cells and the transition to overt hyperglycemia and diabetes.",
keywords = "a-cell volume, b-cell volume, insulin resistance, obesity duration, obesity severity, pancreatic islet remodeling",
author = "R. Guardado-Mendoza and L. Jimenez-Ceja and A. Majluf-Cruz and S. Kamath and Fiorentino, {T. V.} and F. Casiraghi and Velazquez, {A. O C} and Defronzo, {Ralph A} and E. Dick and A. Davalli and F. Folli",
year = "2013",
month = "8",
doi = "10.1038/ijo.2012.205",
language = "English (US)",
volume = "37",
pages = "1071--1078",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Impact of obesity severity and duration on pancreatic β-and α-cell dynamics in normoglycemic non-human primates

AU - Guardado-Mendoza, R.

AU - Jimenez-Ceja, L.

AU - Majluf-Cruz, A.

AU - Kamath, S.

AU - Fiorentino, T. V.

AU - Casiraghi, F.

AU - Velazquez, A. O C

AU - Defronzo, Ralph A

AU - Dick, E.

AU - Davalli, A.

AU - Folli, F.

PY - 2013/8

Y1 - 2013/8

N2 - Objective: Obesity is associated with high insulin and glucagon plasma levels. Enhanced β-cell function and β-cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons. Methods: Pancreatic β-and α-cell volumes were measured in 51 normoglycemic baboons divided into six groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters. Results: Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater increase in RIαV. Baboons' body weights correlated with serum levels of interleukin-6 and tumor necrosis factor-α soluble receptors, demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β-and α-cell viability and replication. Conclusion: In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV), whereas have minimal effects on the β cells. This study suggests that an increase in the α-cell mass may precede the loss of β cells and the transition to overt hyperglycemia and diabetes.

AB - Objective: Obesity is associated with high insulin and glucagon plasma levels. Enhanced β-cell function and β-cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons. Methods: Pancreatic β-and α-cell volumes were measured in 51 normoglycemic baboons divided into six groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters. Results: Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater increase in RIαV. Baboons' body weights correlated with serum levels of interleukin-6 and tumor necrosis factor-α soluble receptors, demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β-and α-cell viability and replication. Conclusion: In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV), whereas have minimal effects on the β cells. This study suggests that an increase in the α-cell mass may precede the loss of β cells and the transition to overt hyperglycemia and diabetes.

KW - a-cell volume

KW - b-cell volume

KW - insulin resistance

KW - obesity duration

KW - obesity severity

KW - pancreatic islet remodeling

UR - http://www.scopus.com/inward/record.url?scp=84881133721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881133721&partnerID=8YFLogxK

U2 - 10.1038/ijo.2012.205

DO - 10.1038/ijo.2012.205

M3 - Article

C2 - 23229736

AN - SCOPUS:84881133721

VL - 37

SP - 1071

EP - 1078

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 8

ER -