The effect of the senescence-associated secretory phenotype (SASP) on glucose homeostasis in metabolic cells

Research output: Contribution to journalMeeting abstract

Abstract

Aim: Dysregulated glucose homeostasis is a hallmark of Type 2diabetes. A distinctive feature of ageing is the accumulation ofsenescent cells, defined as cells that have undergone irreversible lossof proliferative capacity. Characteristic of senescent cells is thesenescence-associated secretory phenotype (SASP) involving theproduction of factors which reinforce senescence arrest in neigh-bouring tissue environments. We hypothesise that SASP inducesmetabolic dysfunction in non-senescent cells, impairing glucosemetabolism and propagating insulin resistance. We sought todetermine the effect of SASP on glucose homeostasis in hepatic,adipose and skeletal muscle cell lines.
Methods: Human dermal fibroblasts were subjected to a geno-toxic dose of doxorubicin to induce senescence, confirmed using ab-galactosidase assay. Conditioned media containing SASP werecollected post 24h and 48h of inducing senescence and used at20% and 40% concentrations to treat AML-12 hepatocytes, 3T3-L1 adipocytes and C2C12 myocytes for 24h and 48h. Cells andmedia were collected and glucose and lipid concentrations weremeasured before and after the respective incubation periods.
Results: Cell media obtained from C2C12 myocytes exposed to40% SASP for 24h and 48h and AML-12 hepatocytes after 48hexhibited significantly higher concentrations of glucose in com-parison to control media (p < 0.0001, p < 0.05) suggesting areduced glucose uptake. Glucose utilisation remained unchanged in3T3-L1 cells.
Conclusion: Our data suggest an important role for SASP inaltering glucose homeostasis and identify SASP as a potentialmediator between ageing and the increase in age-related insulinresistance.
LanguageEnglish
Article numberP208
Pages93-94
Number of pages2
JournalDiabetic Medicine
Volume32
Issue numberSuppl.1
DOIs
Publication statusPublished - 11 Mar 2015
EventDiabetes UK Professional Conference 2015 - ExCel London, London, United Kingdom
Duration: 11 Mar 201513 Mar 2015

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Homeostasis
Phenotype
Glucose
Muscle Cells
Hepatocytes
Galactosidases
Poisons
Conditioned Culture Medium
Adipocytes
Doxorubicin
Insulin Resistance
Skeletal Muscle
Fibroblasts
Lipids
Cell Line
Skin
Liver

Bibliographical note

Special Issue: Abstracts of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.

Cite this

@article{adb49232b16744ca97a84a2d3912bbbb,
title = "The effect of the senescence-associated secretory phenotype (SASP) on glucose homeostasis in metabolic cells",
abstract = "Aim: Dysregulated glucose homeostasis is a hallmark of Type 2diabetes. A distinctive feature of ageing is the accumulation ofsenescent cells, defined as cells that have undergone irreversible lossof proliferative capacity. Characteristic of senescent cells is thesenescence-associated secretory phenotype (SASP) involving theproduction of factors which reinforce senescence arrest in neigh-bouring tissue environments. We hypothesise that SASP inducesmetabolic dysfunction in non-senescent cells, impairing glucosemetabolism and propagating insulin resistance. We sought todetermine the effect of SASP on glucose homeostasis in hepatic,adipose and skeletal muscle cell lines. Methods: Human dermal fibroblasts were subjected to a geno-toxic dose of doxorubicin to induce senescence, confirmed using ab-galactosidase assay. Conditioned media containing SASP werecollected post 24h and 48h of inducing senescence and used at20{\%} and 40{\%} concentrations to treat AML-12 hepatocytes, 3T3-L1 adipocytes and C2C12 myocytes for 24h and 48h. Cells andmedia were collected and glucose and lipid concentrations weremeasured before and after the respective incubation periods. Results: Cell media obtained from C2C12 myocytes exposed to40{\%} SASP for 24h and 48h and AML-12 hepatocytes after 48hexhibited significantly higher concentrations of glucose in com-parison to control media (p < 0.0001, p < 0.05) suggesting areduced glucose uptake. Glucose utilisation remained unchanged in3T3-L1 cells. Conclusion: Our data suggest an important role for SASP inaltering glucose homeostasis and identify SASP as a potentialmediator between ageing and the increase in age-related insulinresistance.",
author = "K.S. Rana and E.J. Hill and S. Bellary and J.E. Brown",
note = "Special Issue: Abstracts of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.",
year = "2015",
month = "3",
day = "11",
doi = "10.1111/dme.12668",
language = "English",
volume = "32",
pages = "93--94",
journal = "Diabetic Medicine",
issn = "0742-3071",
publisher = "Wiley-Blackwell",
number = "Suppl.1",

}

The effect of the senescence-associated secretory phenotype (SASP) on glucose homeostasis in metabolic cells. / Rana, K.S.; Hill, E.J.; Bellary, S.; Brown, J.E.

In: Diabetic Medicine, Vol. 32, No. Suppl.1, P208, 11.03.2015, p. 93-94.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - The effect of the senescence-associated secretory phenotype (SASP) on glucose homeostasis in metabolic cells

AU - Rana, K.S.

AU - Hill, E.J.

AU - Bellary, S.

AU - Brown, J.E.

N1 - Special Issue: Abstracts of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.

PY - 2015/3/11

Y1 - 2015/3/11

N2 - Aim: Dysregulated glucose homeostasis is a hallmark of Type 2diabetes. A distinctive feature of ageing is the accumulation ofsenescent cells, defined as cells that have undergone irreversible lossof proliferative capacity. Characteristic of senescent cells is thesenescence-associated secretory phenotype (SASP) involving theproduction of factors which reinforce senescence arrest in neigh-bouring tissue environments. We hypothesise that SASP inducesmetabolic dysfunction in non-senescent cells, impairing glucosemetabolism and propagating insulin resistance. We sought todetermine the effect of SASP on glucose homeostasis in hepatic,adipose and skeletal muscle cell lines. Methods: Human dermal fibroblasts were subjected to a geno-toxic dose of doxorubicin to induce senescence, confirmed using ab-galactosidase assay. Conditioned media containing SASP werecollected post 24h and 48h of inducing senescence and used at20% and 40% concentrations to treat AML-12 hepatocytes, 3T3-L1 adipocytes and C2C12 myocytes for 24h and 48h. Cells andmedia were collected and glucose and lipid concentrations weremeasured before and after the respective incubation periods. Results: Cell media obtained from C2C12 myocytes exposed to40% SASP for 24h and 48h and AML-12 hepatocytes after 48hexhibited significantly higher concentrations of glucose in com-parison to control media (p < 0.0001, p < 0.05) suggesting areduced glucose uptake. Glucose utilisation remained unchanged in3T3-L1 cells. Conclusion: Our data suggest an important role for SASP inaltering glucose homeostasis and identify SASP as a potentialmediator between ageing and the increase in age-related insulinresistance.

AB - Aim: Dysregulated glucose homeostasis is a hallmark of Type 2diabetes. A distinctive feature of ageing is the accumulation ofsenescent cells, defined as cells that have undergone irreversible lossof proliferative capacity. Characteristic of senescent cells is thesenescence-associated secretory phenotype (SASP) involving theproduction of factors which reinforce senescence arrest in neigh-bouring tissue environments. We hypothesise that SASP inducesmetabolic dysfunction in non-senescent cells, impairing glucosemetabolism and propagating insulin resistance. We sought todetermine the effect of SASP on glucose homeostasis in hepatic,adipose and skeletal muscle cell lines. Methods: Human dermal fibroblasts were subjected to a geno-toxic dose of doxorubicin to induce senescence, confirmed using ab-galactosidase assay. Conditioned media containing SASP werecollected post 24h and 48h of inducing senescence and used at20% and 40% concentrations to treat AML-12 hepatocytes, 3T3-L1 adipocytes and C2C12 myocytes for 24h and 48h. Cells andmedia were collected and glucose and lipid concentrations weremeasured before and after the respective incubation periods. Results: Cell media obtained from C2C12 myocytes exposed to40% SASP for 24h and 48h and AML-12 hepatocytes after 48hexhibited significantly higher concentrations of glucose in com-parison to control media (p < 0.0001, p < 0.05) suggesting areduced glucose uptake. Glucose utilisation remained unchanged in3T3-L1 cells. Conclusion: Our data suggest an important role for SASP inaltering glucose homeostasis and identify SASP as a potentialmediator between ageing and the increase in age-related insulinresistance.

UR - https://onlinelibrary.wiley.com/doi/abs/10.1111/dme.12668

U2 - 10.1111/dme.12668

DO - 10.1111/dme.12668

M3 - Meeting abstract

VL - 32

SP - 93

EP - 94

JO - Diabetic Medicine

T2 - Diabetic Medicine

JF - Diabetic Medicine

SN - 0742-3071

IS - Suppl.1

M1 - P208

ER -