Metformin Plays a Dual Role in MIN6 Pancreatic β Cell Function through AMPK-dependent Autophagy

Abstract

Metformin improves insulin sensitivity in insulin sensitive tissues such as liver, muscle and fat. However, the functional roles and the underlying mechanism of metformin action in pancreatic β cells remain elusive. Here we show that, under normal growth condition, metformin suppresses MIN6 β cell proliferation and promotes apoptosis via an AMPK-dependent and autophagy-mediated mechanism. On the other hand, metformin protects MIN6 cells against palmitic acid (PA)-induced apoptosis. Our findings indicate that metformin plays a dual role in β cell survival and overdose of this anti-diabetic drug itself may lead to potential β cell toxicity.

Effects of addition of a dipeptidyl peptidase IV inhibitor to metformin on sirolimus-induced diabetes mellitus

“…In this study, we studied SRL-induced oxidative stress in animal model (Figure 3 (10)(11)(12)(13)(51)(52)(53). MET also has protective effects on cell viability and ROS production via a variety of mechanisms (54, 55). Taken together, our animal and in vitro study reveals that addition of DPP IV inhibitor to MET provides protection against SRLinduced pancreatic islet injury by decreasing oxidative stress.…”

Enhancement of anti-proliferative activities of Metformin, when combined with Celecoxib, without increasing DNA damage

“…Metformin demotes gluconeogenesis through activation of an upstream kinase, liver kinase B1 (LKB-1) and by inhibiting mitochondrial respiration and ultimately block the energy requirement of gluconeogenesis (Jiang et al, 2014). Recent studies proposed that reduction in hepatic gluconeogenesis by Metformin is through non-competitive inhibition of mitochondrial glycerophosphate dehydrogenase; redox shuttle enzyme, which results in altered redox state of hepatic cells and ultimately the conversion of lactate and glycerol into glucose is reduced (Madiraju et al, 2014).…”

Autophagy: A housekeeper in cardiorenal metabolic health and disease

“…Autophagy removes damaged intracellular macromolecules and organelles and plays a protective role for cell survival [6]. Therefore, autophagy not only plays a principal role in the supply of nutrients for cell survival but also plays a constitutive role in cellular homeostasis by acting as a cytoplasmic quality control mechanism to eliminate old or unfolded proteins and damaged organelles [7].…”