Glibenclamide-Induced Autophagy Inhibits Its Insulin Secretion-Improving Function in β Cells

Abstract

Diabetes is a metabolic disease, partly due to hypoinsulinism, which affects ∼8% of the world’s adult population. Glibenclamide is known to promote insulin secretion by targeting β cells. Autophagy as a self-protective mechanism of cells has been widely studied and has particular physiological effects in different tissues or cells. However, the interaction between autophagy and glibenclamide is unclear. In this study, we investigated the role of autophagy in glibenclamide-induced insulin secretion in pancreatic β cells. Herein, we showed that glibenclamide promoted insulin release and further activated autophagy through the adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) pathway in MIN-6 cells. Inhibition of autophagy with autophagy inhibitor 3-methyladenine (3-MA) potentiated the secretory function of glibenclamide further. These results suggest that glibenclamide-induced autophagy plays an inhibitory role in promoting insulin secretion by activating the AMPK pathway instead of altering the mammalian target of rapamycin (mTOR).

Role of FoxO1 in regulating autophagy in type 2 diabetes mellitus (Review)

“…A recent study reported that pretreatment with rapamycin, an mTOR inhibitor, induces autophagy and significantly decreases the insulin content in NIT-1 cells ( 35 ). Another study reported similar results, indicating that the level of insulin significantly increases due to glibenclamide, and further increases with 3-MA ( 36 ). Collectively, these findings suggest that suppressing autophagy increases β-cell insulin secretion.…”

Golgi-associated Rab GTPases implicated in autophagy

“…Autophagy is important for maintaining cellular homeostasis and is involved in the pathogenesis of a myriad of diseases, such as metabolic disorders, cancers, neurodegenerative diseases, and pathogen infections [ 114 – 117 ]. Interestingly, alteration in Golgi-associated Rab GTPase is also implicated in these diseases.…”

Antihyperglycemic and hypoglycemic activity of Mayan plant foods in rodent models

“…It belongs to the sulfonylurea group and acts to increase insulin secretion by directly closing ATP-sensitive K channels in pancreatic cells, causing depolarization of the membrane, opening Ca 2 + voltage-dependent channels, and leading to intracellular Ca 2+ influx and elevation, triggering insulin exocytosis. 40 Bixa orellana has demonstrated hypoglycemic effects in healthy 41 and diabetic animal models. 42 However, its mechanism of action is still unclear.…”