Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis

Abstract

Background. Hypoglycemia is a dangerous side effect of intensive glucose control in diabetes. Even though it leads to adverse cardiovascular events, the effects of hypoglycemia on vascular biology in diabetes have not been adequately studied. Methods. Aged Sprague-Dawley rats were fed a high-fat diet and given streptozotocin to induce type 2 diabetes mellitus (T2DM). Acute and recurrent hypoglycemia were then induced by glucose via insulin administration. Vascular function, oxidative stress, and pyroptosis levels in aortic tissue were assessed by physiological and biochemical methods. Results. Hypoglycemia was associated with a marked decrease in vascular function, elevated oxidative stress, and elevated pyroptosis levels in the thoracic aorta. The changes in oxidative stress and pyroptosis were greater in rats with recurrent hypoglycemia than in those with acute hypoglycemia. Conclusions. Hypoglycemia impaired vascular function in aged rats with T2DM by inducing pyroptosis. The extent of injury increased with the duration of blood glucose fluctuation.

Puerarin mitigated LPS‐ATP or HG‐primed endothelial cells damage and diabetes‐associated cardiovascular disease via ROS‐NLRP3 signalling

“…Previous studies showed that the anti‐inflammatory properties may contribute to the described cardiovascular benefits of procyanidins. 9 , 10 , 11 , 12 However, the molecular mechanisms underlying the anti‐inflammatory effects of PCB are not fully understood. To investigate the role of Pue in LPS‐ATP‐primed endothelial cells impairment, HUVECs were treated with varying concentration of Pue for 2 h and then exposed to LPS‐ATP for 24 h. LDH, an intracellular enzyme, releases into the cell supernatant upon cell damage.…”

“…Based on the results of the CCK8 assay, 25 and 50 μM Pue was chosen for the most optimal concentration and used in subsequent experiments (Figure 1A). Previous studies showed that the anti‐inflammatory properties may contribute to the described cardiovascular benefits of procyanidins 9–12 . However, the molecular mechanisms underlying the anti‐inflammatory effects of PCB are not fully understood.…”

“…Previous studies showed that the anti-inflammatory properties may contribute to the described cardiovascular benefits of procyanidins. [9][10][11][12] However, the Pue partially reversed this decrease in the ratio of p-eNOS-eNOS (Figure 1H). The above results suggested that Pue has a protective effect on LPS-ATP-primed HUVECs impairment.…”

“…Furthermore, the association between pyroptosis and diabetic retinopathy (DR) is evident, with pyroptosis critically contributing to the adverse effects experienced by cells in the retinal neurovascular unit (NVU) under hyperglycaemic conditions. Moreover, 10 , 11 , 12 , 13 , 14 the activation of the nucleotide oligomerization domain (NOD)‐like receptor (NLR) family, pyrin domain‐containing protein 3 (NLRP3) inflammasomes are associated with the pathogenesis of a wide range of inflammatory diseases. The activation of NLRP3 can facilitate caspase‐1‐mediated proteolytic activation of IL‐1β and IL‐18.…”

Acute severe hypoglycemia alters mouse brain microvascular proteome

“…Hypoglycemia was shown to induce endothelial dysfunction and blood-brain-barrier defects in vitro, but its effect on BMVs was not studied previously. [22][23][24][25][26][27][28][29][30][31][32] Studies focusing on global proteomic changes in the microvasculature in response to hypoglycemia were never reported before.…”