Concerted Trafficking Regulation of Kv2.1 and KATP Channels by Leptin in Pancreatic β-Cells

Wu, Yi; Shyng, Show Ling; Chen, Pei Chun

doi:10.1074/jbc.m115.670877

Cited by 30 publications

(55 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, the effect of trafficking moderated by AMPK will be minimized if the channel is blocked by glibenclamide. Similarly, AMPK also moderates the trafficking of I Kur channel, and the trafficking can also be blocked by compound C 20 . Low concentration 4‐AP blocks I Kur by directly binding to the channel 21 .…”

Section: Discussionmentioning

confidence: 98%

The AMP‐activated protein kinase modulates hypothermia‐induced J wave

Chen

et al. 2020

Eur J Clin Investigation

View full text Add to dashboard Cite

Background:The mechanism underlying the occurrence of the J wave in low temperature remains unclear. However, low temperature is associated with metabolic disorder and 5' AMP-activated protein kinase (AMPK), which modulates ionic currents and cardiac metabolism. This study investigated whether AMPK regulation can modulate the occurrence of the J wave at low temperature. Methods: Unipolar and bipolar leads were used to record monophasic action potential (the endocardium and epicardium) and pseudo-electrocardiograms (inferior leads) to study the cardiac electrical activity. Measurements were taken in isolated Langendorff rabbit hearts at both 30℃ and 37℃ before and after administration of 4-aminopyridine (an ultrarapid delayed rectifier potassium current inhibitor, I Kur , 50 µmol L −1 ), PF06409577 (an AMPK activator, 1 µmol L −1 ), compound C (an AMPK inhibitor, 10 µmol L −1 ) and glibenclamide (an ATP-sensitive inward rectifier potassium channel inhibitor, I KATP , 20 µmol L −1 ). Results: The amplitude of the J wave (2.46 ± 0.34 mV vs. 1.11 ± 0.23 mV, P < .01) at 30℃ (n = 15) was larger than that at 37℃ (n = 15). PF06409577 (1 µmol L −1 ) increased the J waves at both 30℃ and 37℃. In contrast, compound C (10 µmol L −1 ) reduced J wave at both 37℃ and 30℃. Low-temperature-induced J waves were individually suppressed by 4-AP (50 µmol L −1 ) and glibenclamide (20 µmol L −1 ). Conclusions: AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating I KATP and I Kur channels.

show abstract

Section: Discussionmentioning

confidence: 98%

The AMP‐activated protein kinase modulates hypothermia‐induced J wave

Chen

et al. 2020

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…Leptin also induces an increased surface expression of Kv2.1 channels, leading to a rapid repolarization of membrane potential (Park et al, 2013b). These studies suggest that leptin exerts a coordinated trafficking regulation of K ATP and Kv2.1 channels to inhibit insulin secretion (Wu et al, 2015). Furthermore, leptin activates the AMP-activated protein kinase (AMPK) through phosphorylation by the Ca 21 /calmodulin-dependent protein kinase kinase beta and increases K ATP channels trafficking (Park et al, 2013a).…”

Section: Pharmacology Of K Atp Channels In Pancreatic Beta Cellsmentioning

confidence: 96%

“…The mechanism by which leptin activates K ATP channels involves phosphatase and tensin homologe inhibition mediated by phosphoinositide 3 kinase. phosphatase and tensin homologe inhibition induces F-actin depolymerization and, consequently, K ATP channel opening (Park et al, 2013b;Wu et al, 2015).…”

Section: Endogenous Regulation Of K Atp Channels In the Beta Cellmentioning

confidence: 99%

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

et al. 2016

View full text Add to dashboard Cite

Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (K ATP ) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na 1 channels (Nav) and subsequently voltage-dependent Ca 21 channels (Cav).The increase in intracellular Ca 21 triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (K ATP , Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion.

show abstract

“…1). 13,33,[41][42][43][44][45] Furthermore, leptin is shown to promote K ATP channels trafficking from cytosolic vesicles to the plasma membrane of b-cells through the stimulation of AMP-activated protein kinase (AMPK). 33,42,46 Thus, in general, leptin hyperpolarizes both anorexigenic neurons and pancreatic b-cells through activation of K ATP conductances.…”

Section: Downregulation Of G-enac Expressionmentioning

confidence: 99%

Leptin-mediated ion channel regulation: PI3K pathways, physiological role, and therapeutic potential

2016

View full text Add to dashboard Cite

Leptin is produced by adipose tissue and identified as a "satiety signal," informing the brain when the body has consumed enough food. Specific areas of the hypothalamus express leptin receptors (LEPRs) and are the primary site of leptin action for body weight regulation. In response to leptin, appetite is suppressed and energy expenditure allowed. Beside this hypothalamic action, leptin targets other brain areas in addition to neuroendocrine cells. LEPRs are expressed also in the hippocampus, neocortex, cerebellum, substantia nigra, pancreatic β-cells, and chromaffin cells of the adrenal gland. It is intriguing how leptin is able to activate different ionic conductances, thus affecting excitability, synaptic plasticity and neurotransmitter release, depending on the target cell. Most of the intracellular pathways activated by leptin and directed to ion channels involve PI3K, which in turn phosphorylates different downstream substrates, although parallel pathways involve AMPK and MAPK. In this review we will describe the effects of leptin on BK, KATP, KV, CaV, TRPC, NMDAR and AMPAR channels and clarify the landscape of pathways involved. Given the ability of leptin to influence neuronal excitability and synaptic plasticity by modulating ion channels activity, we also provide a short overview of the growing potentiality of leptin as therapeutic agent for treating neurological disorders.

show abstract

Concerted Trafficking Regulation of Kv2.1 and KATP Channels by Leptin in Pancreatic β-Cells

Cited by 30 publications

References 67 publications

The AMP‐activated protein kinase modulates hypothermia‐induced J wave

The AMP‐activated protein kinase modulates hypothermia‐induced J wave

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

Leptin-mediated ion channel regulation: PI3K pathways, physiological role, and therapeutic potential

Contact Info

Product

Resources

About