Format

Send to

Choose Destination
See comment in PubMed Commons below
J Surg Res. 2013 Aug;183(2):944-951. doi: 10.1016/j.jss.2013.02.055. Epub 2013 Mar 19.

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

Author information

1
Division of Vascular Surgery and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
2
Jesse Brown VA Medical Center, Chicago, Illinois.
#
Contributed equally

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

PMID:
23608617
PMCID:
PMC3964777
DOI:
10.1016/j.jss.2013.02.055
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Support Center