<<snip>>
oxidative stress may indeed be involved in the pathogenesis of certain types of
insulin resistance
<<snip>>
Horm Metab Res. 2004 Aug;36(8):542-9. Related Articles, Links
alpha-lipoic Acid Mitigates Insulin Resistance in Goto-Kakizaki Rats.
Bitar MS, Wahid S, Pilcher CW, Al-Saleh E, Al-Mulla F.
Department of Pharmacology & Toxicology, Kuwait University, Faculty of
Medicine, Safat, Kuwait.
Impaired glucose uptake and metabolism by peripheral tissues is a common
feature in both type I and type II diabetes mellitus. This phenomenon was
examined in the context of oxidative stress and the early events within the
insulin signalling pathway using soleus muscles derived from non-obese,
insulin-resistant type II diabetic Goto-Kakizaki (GK) rats, a well-known
genetic rat model for human type II diabetes. Insulin-stimulated glucose
transport was impaired in soleus muscle from GK rats. Oxidative and
non-oxidative glucose disposal pathways represented by glucose oxidation and
glycogen synthesis in soleus muscles of GK rats appear to be resistant to the
action of insulin when compared to their corresponding control values. These
diabetes-related abnormalities in glucose disposal were associated with a
marked diminution in the insulin-mediated enhancement of protein kinase B
(Akt/PKB) and insulin receptor substrate-1 (IRS-1)-associated
phosphatidylinostol 3-kinase (PI 3-kinase) activities; these two kinases are
key elements in the insulin signalling pathway. Moreover, heightened state of
oxidative stress, as indicated by protein bound carbonyl content, was evident
in soleus muscle of GK diabetic rats. Chronic administration of the
hydrophobic/hydrophilic antioxidant alpha -lipoic-acid (ALA, 100 mg/kg, ip)
partly ameliorated the diabetes-related deficit in glucose metabolism, protein
oxidation as well as the activation by insulin of the various steps of the
insulin signalling pathway, including the enzymes Akt/PKB and PI-3 kinase.
Overall, the current investigation illuminates the concept that oxidative
stress may indeed be involved in the pathogenesis of certain types of insulin
resistance. It also harmonizes with the notion of including potent antioxidants
such as ALA in the armamentarium of antidiabetic therapy.
PMID: 15326564 [PubMed - in process]
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