Abstract
Chronic exposure of pancreatic β-cells to elevated nutrient levels impairs their function and potentially induces apoptosis. Like in other cell types, AMPK is activated in β-cells under conditions of nutrient deprivation, while little is known on AMPK responses to metabolic stresses. Here, we first reviewed recent studies on the role of AMPK activation in β-cells. Then, we investigated the expression profile of AMPK pathways in β-cells following metabolic stresses. INS-1E β-cells and human islets were exposed for 3 days to glucose (5.5–25 mM), palmitate or oleate (0.4 mM), and fructose (5.5 mM). Following these treatments, we analyzed transcript levels of INS-1E β-cells by qRT-PCR and of human islets by RNA-Seq; with a special focus on AMPK-associated genes, such as the AMPK catalytic subunits α1 (Prkaa1) and α2 (Prkaa2). AMPKα and pAMPKα were also evaluated at the protein level by immunoblotting. Chronic exposure to the different metabolic stresses, known to alter glucose-stimulated insulin secretion, did not change AMPK expression, either in insulinoma cells or in human islets. Expression profile of the six AMPK subunits was marginally modified by the different diabetogenic conditions. However, the expression of some upstream kinases and downstream AMPK targets, including K-ATP channel subunits, exhibited stress-specific signatures. Interestingly, at the protein level, chronic fructose treatment favored fasting-like phenotype in human islets, as witnessed by AMPK activation. Collectively, previously published and present data indicate that, in the β-cell, AMPK activation might be implicated in the pre-diabetic state, potentially as a protective mechanism.
Highlights
We reported that chronic fructose exposure induces AMPK activation in the β-cell [12], indicating that this sugar, as opposed to glucose, promotes a paradoxical intracellular fasting-like phenotype
TthheosAeMinPclKuαd/eβ tihnetesreaccrteotmoreywreesrpeoindseen,ticfeielldulaanrddaesvseolocipamtedentto, dβi-ffceelrlenfutinacttioionn,scwelhl–ecnellgrcooumpmeduninictoatigoenneanodntaoclotigny otregramnsi.zaTtihoons, eilluinstcrlautdineg tthhee bsreocardetroarnygeroesfpfuonncseti,oncselmlueldariatdedevbeyloApMmePnKt,acdtiivffietyr.entiation, cell–cell communication and actin organization, illustrating the broad range of functions mediated by AMPK 2a.2c.tiDviitayb.etogenic Conditions do not Alter AMPK Gene Expression in INS-1E β-Cells and Human Islets
We recently reported that chronic fructose exposure on pancreatic β-cells results in AMPK activation and exaggerated insulin secretion, even at intermediate glucose concentrations [12]
Summary
Insulin regulates blood glucose through its action on its target tissues, promoting storage of metabolic substrates and energy homeostasis. In the context of obesity, insulin becomes less efficient as a consequence of the development of insulin resistance by the target tissues Such resistance can be counterbalanced by increased production of insulin by the pancreatic β-cells. Defects in the insulin-producing cells represent the triggering event leading to hyperglycemia that characterizes type 2 diabetes [2]. In these pathogenic conditions, AMPK pathways might play a role in the preservation of functional β-cells [3]. Growing evidence indicate that AMPK is involved in whole-body glucose homeostasis, potentially as a positive and negative modulator of insulin secretion from β-cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
