RESUMO
Normal glucose metabolism is critical to immune function but the effects of short-term hyperglycemia on immunity are not well described. To study this phenomenon, we induced hyperglycemia in healthy subjects for 2 h with intravenous dextrose and octreotide. An RNA-seq analysis of whole blood RNA demonstrated alterations in multiple immune pathways and transcripts during acute hyperglycemia including decreased transcription of IL-6, an important component of both innate and adaptive immune responses. Additional in vitro studies of human peripheral blood mononuclear cells (PBMCs) exposed to high glucose confirmed decreased IL-6 expression, most prominently in CD14(+)CD16(+) intermediate monocytes. Hyperglycemia also reduced IL-17A expression suggesting further impairment of immune responses during acute hyperglycemia. These findings demonstrate multiple defective immune responses in acute hyperglycemia and suggest a novel role for intermediate monocytes as metabolically sensitive innate immune cells.
RESUMO
The diabetes prevention trial-type 1 (DPT-1) tested whether a combination of SQ and IV insulin therapy would delay the onset of disease in individuals at high risk of progression. We investigated whether this regimen altered T cell responses to human islet proteins using cellular immunoblotting. Among the 10 treated and 7 control subjects studied, we found that there was a significant effect of treatment on cellular immunoblotting responses. We conclude that parenteral insulin may suppress proliferation to islet antigens in individuals at risk for diabetes, but this effect may be transient. Further study is needed to determine whether a therapy that results in sustained suppression of T cell proliferation could yield a measurable clinical benefit.
