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Insulin Autoimmune Syndrome (IAS) is a rare disease characterized by hypoglycemia and autoantibodies to insulin without prior insulin administration. Here, we report a case of IAS associated with alpha lipoic acid (ALA). The patient is a 55-year-old man. He began to complain of hypoglycemic symptoms after taking ALA. He lost consciousness in the late postprandial period and blood glucose was found to be 27 mg/dl. A high insulin level and high titers of insulin antibodies were detected. His HLA genotype contains DRB1* 0406. As ALA comes to be used widely, the incidence of IAS due to ALA might increase.

Because vascular endothelial cell growth factor (VEGF) and transforming growth factor-beta (TGF-beta) are both involved in cellular growth and differentiation, we examined whether VEGF modifies TGF-beta signaling cascade in human umbilical cord vein endothelial cells (HUVEC). Production of plasminogen activator inhibitor-1 (PAI-1), which is under the specific control of TGF-beta, was strongly enhanced (3.5-fold) by TGF-beta treatment. Remarkably, physiological concentration of VEGF (30 nm) profoundly (by 60%) attenuated the TGF-beta stimulation of PAI-1 production without an effect on the basal PAI-1 production. In HUVECs transiently transfected with an expression construct containing a PAI-1 promoter fused to luciferase reporter gene, TGF-beta-stimulation of transcription of PAI-1 was clearly (by 60%) inhibited by VEGF. TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action in the human endothelial cell, specifically at the level of transcription of PAI-1 gene and Smad2/3 phosphorylation.