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Moxonidine as an Insulin Sensitizing Agent
Author(s) -
Edwards Lincoln Paul,
Cheema Meherali,
Nunemaker Craig
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1169.11
Subject(s) - moxonidine , insulin , islet , imidazoline receptor , pharmacology , endocrinology , chemistry , protein kinase b , insulin receptor , medicine , phosphorylation , receptor , insulin resistance , biochemistry , agonist
Oral medications used to treat type 2 diabetes have important adverse effects. Novel agents with fewer risks are needed. Published studies indicate that moxonidine can have insulin sensitizing effects. The objective of this study is to provide insight into the mechanism(s) by which moxonidine acts as an insulin sensitizing agent. The acute and chronic effects of moxonidine on calcium handling by islet cells were determined in vitro using isolated mouse pancreatic islets. Time‐course and dose‐response studies were also carried out in cells, followed by Western blotting. Moxonidine lowered calcium levels in islet cells in a manner that was dose‐dependent up to 10nM, reversible and independent of the K ATP channel. Moxonidine [1μM] caused an increased phosphorylation of both protein kinase B (PKB) and protein dependent kinase (PDK) by greater than 3 fold in HepG2 and HEK293 cells. The increased PKB phosphorylation could be blocked by efaroxan (10μM). Cells overexpressing the imidazoline receptor protein IRAS, showed greater phosphorylation of PKB compared to control, following moxonidine treatment. Moxonidine caused a time‐dependent increase in glucose uptake in HepG2 cells of up to 2.5 fold, and this could be blocked by efaroxan and by phosphatidyl inositol‐3‐ kinase inhibitor LY294002. These data suggests that moxonidine may regulate islet insulin release while sensitizing tissues to the action of insulin. These studies were supported in part by NIH1R15DK084468–01 A1and the Center for Health Disparities at Loma Linda University