Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats

Monica P. Rodriguez; Zachary M. Emond; Vinit N. Varu; Sadaf S. Ahanchi; Janet Martinez; Melina R. Kibbe

doi:10.1016/j.jss.2013.02.055

Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats

Monica P. Rodriguez, Zachary M. Emond, Vinit N. Varu, Sadaf S. Ahanchi, Janet Martinez, Melina R. Kibbe^*

^*Corresponding author for this work

Surgery, Vascular Surgery Division

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Background: We have shown that nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia in type 2 diabetic rats than in nondiabetic rats, but is not effective in type 1 diabetic rats. Insulin signaling is mediated by the ERK and Akt pathways, and thus we hypothesized that NO differentially affects ERK and Akt activity in type 1 versus type 2 diabetic rats. Materials and methods: To investigate this hypothesis, we induced type 2 diabetes in Zucker diabetic fatty (ZDF) rats by feeding them Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60 mg/kg). The carotid artery injury model was performed. Groups included injury and injury + PROLI/NO (20 mg/kg) (n = 6/group). Results: Three days following injury, all animal models exhibited an increase in pERK levels. Whereas NO reduced pERK levels in LZ and STZ rats, NO had no effect on pERK levels in ZDF rats. Following a similar pattern, NO reduced pAkt levels in LZ and STZ rats but increased pAkt levels in ZDF rats. Fourteen days following injury, NO increased total pERK levels throughout the arterial wall in both the STZ and ZDF rats. These changes were greatest in the adventitia. Interestingly, whereas NO decreased total pAkt levels in LZ and STZ rats, NO increased pAkt levels in ZDF rats. Evaluation of the pERK:pAkt ratio revealed that NO increased this ratio in LZ and STZ rats but decreased the ratio in ZDF rats. Conclusions: We report that NO differentially affects the expression of pERK and pAkt in type 1 versus type 2 diabetic rats. Given that NO is more effective at inhibiting neointimal hyperplasia in type 2 diabetic animals, the pERK:pAkt ratio may be the best surrogate to predict efficacy.

Original language	English (US)
Pages (from-to)	944-951
Number of pages	8
Journal	Journal of Surgical Research
Volume	183
Issue number	2
DOIs	https://doi.org/10.1016/j.jss.2013.02.055
State	Published - Aug 2013

Funding

Funding: This work was supported in part by funding from the Department of Veterans Affairs, VA Merit Review Grant ( I01 BX000409, MRK ), the Eleanor B. Pillsbury Grant-University of Illinois , the American Medical Association Foundation Seed Grant program (MPR, SSA, VNV), and the Ethicon–Society of University Surgeons Scholarship Award (MPR) , and by the generosity of Mrs Hilda Rosenbloom and Mrs Eleanor Baldwin.

Keywords

Akt
ERK
Metabolic environment
Neointimal hyperplasia
Nitric oxide
Type 1 diabetes
Type 2 diabetes

ASJC Scopus subject areas

Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jss.2013.02.055

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@article{c1419ececfb2473ebcf422c8a998ca74,

title = "Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats",

abstract = "Background: We have shown that nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia in type 2 diabetic rats than in nondiabetic rats, but is not effective in type 1 diabetic rats. Insulin signaling is mediated by the ERK and Akt pathways, and thus we hypothesized that NO differentially affects ERK and Akt activity in type 1 versus type 2 diabetic rats. Materials and methods: To investigate this hypothesis, we induced type 2 diabetes in Zucker diabetic fatty (ZDF) rats by feeding them Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60 mg/kg). The carotid artery injury model was performed. Groups included injury and injury + PROLI/NO (20 mg/kg) (n = 6/group). Results: Three days following injury, all animal models exhibited an increase in pERK levels. Whereas NO reduced pERK levels in LZ and STZ rats, NO had no effect on pERK levels in ZDF rats. Following a similar pattern, NO reduced pAkt levels in LZ and STZ rats but increased pAkt levels in ZDF rats. Fourteen days following injury, NO increased total pERK levels throughout the arterial wall in both the STZ and ZDF rats. These changes were greatest in the adventitia. Interestingly, whereas NO decreased total pAkt levels in LZ and STZ rats, NO increased pAkt levels in ZDF rats. Evaluation of the pERK:pAkt ratio revealed that NO increased this ratio in LZ and STZ rats but decreased the ratio in ZDF rats. Conclusions: We report that NO differentially affects the expression of pERK and pAkt in type 1 versus type 2 diabetic rats. Given that NO is more effective at inhibiting neointimal hyperplasia in type 2 diabetic animals, the pERK:pAkt ratio may be the best surrogate to predict efficacy.",

keywords = "Akt, ERK, Metabolic environment, Neointimal hyperplasia, Nitric oxide, Type 1 diabetes, Type 2 diabetes",

author = "Rodriguez, {Monica P.} and Emond, {Zachary M.} and Varu, {Vinit N.} and Ahanchi, {Sadaf S.} and Janet Martinez and Kibbe, {Melina R.}",

note = "Funding Information: Funding: This work was supported in part by funding from the Department of Veterans Affairs, VA Merit Review Grant ( I01 BX000409, MRK ), the Eleanor B. Pillsbury Grant-University of Illinois , the American Medical Association Foundation Seed Grant program (MPR, SSA, VNV), and the Ethicon–Society of University Surgeons Scholarship Award (MPR) , and by the generosity of Mrs Hilda Rosenbloom and Mrs Eleanor Baldwin.",

year = "2013",

month = aug,

doi = "10.1016/j.jss.2013.02.055",

language = "English (US)",

volume = "183",

pages = "944--951",

journal = "Journal of Surgical Research",

issn = "0022-4804",

publisher = "Academic Press Inc.",

number = "2",

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TY - JOUR

T1 - Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats

AU - Rodriguez, Monica P.

AU - Emond, Zachary M.

AU - Varu, Vinit N.

AU - Ahanchi, Sadaf S.

AU - Martinez, Janet

AU - Kibbe, Melina R.

N1 - Funding Information: Funding: This work was supported in part by funding from the Department of Veterans Affairs, VA Merit Review Grant ( I01 BX000409, MRK ), the Eleanor B. Pillsbury Grant-University of Illinois , the American Medical Association Foundation Seed Grant program (MPR, SSA, VNV), and the Ethicon–Society of University Surgeons Scholarship Award (MPR) , and by the generosity of Mrs Hilda Rosenbloom and Mrs Eleanor Baldwin.

PY - 2013/8

Y1 - 2013/8

N2 - Background: We have shown that nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia in type 2 diabetic rats than in nondiabetic rats, but is not effective in type 1 diabetic rats. Insulin signaling is mediated by the ERK and Akt pathways, and thus we hypothesized that NO differentially affects ERK and Akt activity in type 1 versus type 2 diabetic rats. Materials and methods: To investigate this hypothesis, we induced type 2 diabetes in Zucker diabetic fatty (ZDF) rats by feeding them Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60 mg/kg). The carotid artery injury model was performed. Groups included injury and injury + PROLI/NO (20 mg/kg) (n = 6/group). Results: Three days following injury, all animal models exhibited an increase in pERK levels. Whereas NO reduced pERK levels in LZ and STZ rats, NO had no effect on pERK levels in ZDF rats. Following a similar pattern, NO reduced pAkt levels in LZ and STZ rats but increased pAkt levels in ZDF rats. Fourteen days following injury, NO increased total pERK levels throughout the arterial wall in both the STZ and ZDF rats. These changes were greatest in the adventitia. Interestingly, whereas NO decreased total pAkt levels in LZ and STZ rats, NO increased pAkt levels in ZDF rats. Evaluation of the pERK:pAkt ratio revealed that NO increased this ratio in LZ and STZ rats but decreased the ratio in ZDF rats. Conclusions: We report that NO differentially affects the expression of pERK and pAkt in type 1 versus type 2 diabetic rats. Given that NO is more effective at inhibiting neointimal hyperplasia in type 2 diabetic animals, the pERK:pAkt ratio may be the best surrogate to predict efficacy.

AB - Background: We have shown that nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia in type 2 diabetic rats than in nondiabetic rats, but is not effective in type 1 diabetic rats. Insulin signaling is mediated by the ERK and Akt pathways, and thus we hypothesized that NO differentially affects ERK and Akt activity in type 1 versus type 2 diabetic rats. Materials and methods: To investigate this hypothesis, we induced type 2 diabetes in Zucker diabetic fatty (ZDF) rats by feeding them Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60 mg/kg). The carotid artery injury model was performed. Groups included injury and injury + PROLI/NO (20 mg/kg) (n = 6/group). Results: Three days following injury, all animal models exhibited an increase in pERK levels. Whereas NO reduced pERK levels in LZ and STZ rats, NO had no effect on pERK levels in ZDF rats. Following a similar pattern, NO reduced pAkt levels in LZ and STZ rats but increased pAkt levels in ZDF rats. Fourteen days following injury, NO increased total pERK levels throughout the arterial wall in both the STZ and ZDF rats. These changes were greatest in the adventitia. Interestingly, whereas NO decreased total pAkt levels in LZ and STZ rats, NO increased pAkt levels in ZDF rats. Evaluation of the pERK:pAkt ratio revealed that NO increased this ratio in LZ and STZ rats but decreased the ratio in ZDF rats. Conclusions: We report that NO differentially affects the expression of pERK and pAkt in type 1 versus type 2 diabetic rats. Given that NO is more effective at inhibiting neointimal hyperplasia in type 2 diabetic animals, the pERK:pAkt ratio may be the best surrogate to predict efficacy.

KW - Akt

KW - ERK

KW - Metabolic environment

KW - Neointimal hyperplasia

KW - Nitric oxide

KW - Type 1 diabetes

KW - Type 2 diabetes

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SN - 0022-4804

VL - 183

SP - 944

EP - 951

JO - Journal of Surgical Research

JF - Journal of Surgical Research

IS - 2

ER -

Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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