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The impact of local anesthetics on the regulation of glucose homeostasis by protein kinase B (Akt) and 5′-adenosine monophosphate–activated protein kinase (AMPK) is unclear but important because of the implications for both local anesthetic toxicity and its reversal by IV lipid emulsion (ILE).

Sprague–Dawley rats received 10 mg/kg bupivacaine over 20 s followed by nothing or 10 ml/kg ILE (or ILE without bupivacaine). At key time points, heart and kidney were excised. Glycogen content and phosphorylation levels of Akt, p70 s6 kinase, s6, insulin receptor substrate-1, glycogen synthase kinase-3β, AMPK, acetyl-CoA carboxylase, and tuberous sclerosis 2 were quantified. Three animals received Wortmannin to irreversibly inhibit phosphoinositide-3-kinase (Pi3k) signaling. Isolated heart studies were conducted with bupivacaine and LY294002—a …