Acetylcholinesterase is associated with apoptosis in β cells and contributes to insulin-dependent diabetes mellitus pathogenesis

Abstract

Acetylcholinesterase (AChE) expression is pivotal during apoptosis. Indeed, AChE inhibitors partially protect cells from apoptosis. Insulin-dependent diabetes mellitus (IDDM) is characterized in part by pancreatic b-cell apoptosis. Here, we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors. Multiple low-dose streptozotocin (MLD-STZ) administration resulted in IDDM in a mouse model. Western blot analysis, cytochemical staining, and immunofluorescence staining were used to detect AChE expression in MIN6 cells, primary b cells, and apoptotic pancreatic b cells of MLD-STZ-treated mice. AChE inhibitors were administered intraperitoneally to the MLD-STZ mice for 30 days. Blood glucose, plasma insulin, and creatine levels were measured, and glucose tolerance tests were performed. The effects of AChE inhibitors on MIN6 cells were also evaluated. AChE expression was induced in the apoptotic MIN6 cells and primary b cells in vitro and pancreatic islets in vivo when treated with STZ. Induction and progressive accumulation of AChE in the pancreatic islets were associated with apoptotic b cells during IDDM development. The administration of AChE inhibitors effectively decreased hyperglycemia and incidence of diabetes, and restored plasma insulin levels and plasma creatine clearance in the MLD-STZ mice. AChE inhibitors partially protected MIN6 cells from the damage caused by STZ treatment. Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of IDDM indicate a close relationship between AChE and IDDM.

Insulin/IGF1 signalling mediates the effects of β2‐adrenergic agonist on muscle proteostasis and growth

“…Similar to fasted mice, FOR was able to rescue the low serum INS levels (Figure M) and induced an approximately 2‐fold increase in the muscle phosphorylation levels of Akt, FoxO1, ERK1/2, and CREB (Figure H–L) at 30 min in 3‐day STZ mice. Because it has been described that STZ reduces but does not eliminate INS from mouse pancreas, it is likely that the rise in INS levels caused by β 2 ‐AR stimulation in STZ‐treated mice comes from the remaining β‐pancreatic cells. To further evaluate the role of INS in the anti‐catabolic effects of FOR, muscle‐specific INS receptor (IR) knockout mice (M‐IR −/− ), which exhibit a muscle‐specific ablation of IR signalling, were fasted and then treated with FOR or saline.…”

Effect of Calendula officinalis hydroalcoholic extract on passive avoidance learning and memory in streptozotocin-induced diabetic rats

“…[39] Flowers are also found to contain lycopene and beta-carotene. Coumarins are also active constituents in CO.[40] These constituents may contribute to the antioxidant potential of this extract. The administration of acetylcholinesterase (AChE) inhibitors effectively decreased hyperglycemia and incidence of diabetes, and restored plasma insulin levels and plasma creatinine clearance.…”

“…Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of type 1 diabetes indicate a close relationship between AChE and type 1 diabetes. [40] AChE inhibitors enhance cholinergic function in the brain when loss or decline in memory and cognitive impairment has occurred. [4142] Polyphenols have shown AChE inhibitory effect[43] and considering that CO contains flavonoids,[36] another possible mechanism of CO effect on PAL can be involved in AChE inhibitory potential of the plant.…”

Ecotoxicological Effect of Single and Combined Exposure of Carbamazepine and Cadmium on Female Danio rerio: A Multibiomarker Study

“…Interestingly, the present study showed that AChE activity in zebrafish was enhanced when exposed to combined stress of Cd and CBZ. The increase of AChE activity has been related to the production of free radicals [48] and to the apoptotic processes occurring in the organism [49,50]. AChE activity increase leads to fast acetylcholine degradation and downregulation of acetylcholine receptors, influencing the cognitive functions of the organism [51].…”