<i>In vitro</i> experiments in rat macrophages showed that hyperglycemia treatment suppresses Nrf2 activation, resulting in oxidative stress with decreased expression of antioxidant genes, including NAD(P)H:quinone oxidoreductase 1 and heme oxygenase 1, together with increased secretion of proinflammatory cytokines, including interleukin 1β (IL1β), IL6, and monocyte chemoattractant protein-1.
IL-1β is produced mainly by monocytes (MO), and hyperglycaemia may be able to modulate, in the cytoplasm of these cells, the assembly of a nucleotide-binding domain and leucine-rich repeat containing family pyrin (NLRP3)-inflammosome, a cytosolic multi-protein platform where the inactive pro-IL-1β is cleaved into active form, via caspase-1 activity.
Acute hyperglycemia was shown to promote gene expression of proinflammatory cytokines (il1β, il6, il8, and tnfα) in the brain and chronic hyperglycemia to impair expression of genes involved in the establishment of the blood-brain barrier (claudin 5a, zona occludens 1a and b).
Changes in expression of IL1B, early growth response gene 3, and prostaglandin-endoperoxide synthase 2 resolved within 4 months of insulin therapy and were also observed in T2D, suggesting that they resulted from hyperglycemia.
Downregulation of IL1R1 in individuals with mild hyperglycemia may indicate an attempt to reduce the pro-inflammatory effects of IL-1β via auto-stimulation.
Furthermore, CORM-3-treated mice showed substantial reduction in IL-1β production by hyperglycemia in a mouse model of streptozotocin (STZ)-induced diabetes.
Hyperglycemia in streptozotocin-induced diabetes leads to persistent inflammation and tissue damage following uveitis due to reduced levels of ciliary body heme oxygenase-1.
Importantly, it was found that GF promoted the expression of TNF-α and IL-1β in the hippocampus of the GF rats while continuous hyperglycemia in CHG rats had little effect on that.
In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A2B siRNA abolished these effects.
In primary cultured human brain microvascular endothelial cells (HBMEC), hyperglycemia (25 mM glucose) plus interleukin 1 beta (20 ng/ml) (HG-IL1β) served as T2DM insult in vitro.
In this study, we examined the underlying mechanisms of secreting IL-1β during hyperglycemia, with a focus on the alteration of Ca<sup>2+</sup> homeostasis and lysosomal exocytosis.
In this study, we set out to investigate whether hyperglycemia drives IL-1β production and caspase-1 activation in murine and human adipose tissue, thus inducing insulin resistance.
Our findings reveal a novel mechanism of acute hyperglycemia postburn in which impaired insulin secretory capacity mediated by IL-1β leads to acute hyperglycemia.
Our results showed that hyperglycemia greatly increased inflammation in diabetic rats or HRECs exposed to high glucose, increasing the levels of caspase-1, interleukin-1β (IL-1β) and IL-18.
The hyperglycemia can directly promote an inflammatory state where the increase C-reactive (CRP) and cytokines, such as interleukins (IL-1 and IL-6), which contribute to the development of cardiovascular diseases.
The untreated diabetic group showed hyperglycemia and increased diuresis, creatinine clearance, proteinuria, glycosuria and urinary excretion of <i>N</i>-acetyl-β-d-glucosaminidase (NAG), as well as increased oxidative stress and the expression of interleukin 1β (IL-1β), IL-6, nuclear factor kappa beta (NFκβ) and transforming growth factor-β1 (TGF-β1) in plasma and kidney.
These findings together show that SMR acts as a protector against HG-related stresses not only by lowering hyperglycemia but also suppressing HG- and inflammasome-mediated IL-1β expressions to improve insulin resistance.
This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels.
To understand more about the molecular events that reduce insulin gene transcription, we examined the effects of hyperglycemia alone and together with the proinflammatory cytokine interleukin-1beta (IL-1beta) on signal transduction pathways that regulate insulin gene transcription.