Human transcriptome analysis of acute responses to glucose ingestion reveals the role of leukocytes in hyperglycemia-induced inflammation

Abstract

BG. Human transcriptome analysis of acute responses to glucose ingestion reveals the role of leukocytes in hyperglycemia-induced inflammation. Physiol Genomics 44: 1179 -1187, 2012. First published October 16, 2012 doi:10.1152/physiolgenomics.00179.2011.-Glucose ingestion-induced hyperglycemia has been known to induce inflammation, which is related to the pathogenesis of diabetic complications. To examine acute gene expression responses to physiological oral glucose ingestion in human circulating leukocytes, we conducted a microarray study of human circulating leukocytes sampled before, 1 h after, and 2 h after glucose ingestion in community-based participants without previous histories of diabetes (n ϭ 60). Ingestion of 75 g glucose successfully induced acute hyperglycemia (glucose concentration 91.6 Ϯ 5.3 mg/dl for fasting and 180.7 Ϯ 48.5 mg/dl for 1 h after glucose ingestion). Oral glucose ingestion significantly increased the expressions of 23 genes and decreased the expressions of 13 genes [false discovery rate (FDR) P value Ͻ0.05]. These genes are significantly involved in immunity by way of natural killer cell-mediated immunity, granulocyte-mediated immunity, and the cytokine-mediated signaling pathway (FDR P value Ͻ0.05). The present study demonstrated 36 genes that showed acute gene expression change in human leukocytes within 1 h after glucose ingestion, suggesting that leukocytes participate in the inflammatory process induced by acute hyperglycemia. We believe that these results will provide some basic insight into the role of leukocytes in hyperglycemia-induced inflammation and the pathogenesis of diabetic complications.

Integrative network analysis reveals molecular mechanisms of blood pressure regulation

“…Intravenous infusion of sodium nitroprusside induced hypotension, and the number of Fos‐positive spinal sympathetic neurons increased (Minson et al , ). Several additional BP signature genes have been reported to be involved in BP‐related diseases or processes such as cardiovascular disease (e.g., ABCA1 (Tang & Oram, ), AHR (Zhang, ), and GZMB (Joehanes et al , ,b)), type II diabetes (e.g., ABCA1 (Tang & Oram, ), ANXA1 (Lindgren et al , ), and PTGS2 (Shanmugam et al , )), and inflammation (e.g., GZMB (Hiebert & Granville, ) and KLRD1 (Choi et al , )). We speculate that these genes may play important roles in BP regulation, but further mechanistic studies are necessary.…”

“…The nodes marked with a red border indicate differentially expressed genes between wild-type (WT) and Sh2b3 À/À mice. (Lindgren et al, 2001), and PTGS2 (Shanmugam et al, 2006)), and inflammation (e.g., GZMB (Hiebert & Granville, 2012) and KLRD1 (Choi et al, 2012)). We speculate that these genes may play important roles in BP regulation, but further mechanistic studies are necessary.…”

Inflammation and Hyperglycemia Mediate Deaf1 Splicing in the Pancreatic Lymph Nodes via Distinct Pathways During Type 1 Diabetes

“…5 I and L ). Changes in Ptbp2 expression may be mediated indirectly by hyperglycemia-induced inflammation because hyperglycemia activates various inflammatory pathways, and improper glucose handling is linked with subclinical inflammation ( 41 – 45 ). This would be consistent with the increased Ptbp2 observed in islets after treatment with IFN-γ and IL-1β ( 29 ).…”

Differential DNA methylation of MSI2 and its correlation with diabetic traits

“…For the OGTT assay, the subjects were given 75 g glucose dissolved in 300 ml water (Glucola; Allegiance Healthcare, McGaw Park, IL) to drink within a period of 5 min. Blood samples were obtained at 0, 1, and 2 h after glucose ingestion [6, 20]. Homeostasis Model Assessment (HOMA) was used to estimate insulin resistance (HOMA-IR: Ins0 (μU/mL) × Glu0 (mg/mL)/405).…”