AKAP79/150 coordinates leptin-induced PKA signaling to regulate KATP channel trafficking in pancreatic β-cells

Cochrane, Veronica A.; Yang, Zhongying; Dell’Acqua, Mark L.; Shyng, Show Ling

doi:10.1016/j.jbc.2021.100442

Cited by 11 publications

(7 citation statements)

References 83 publications

(135 reference statements)

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“…PKA also phosphorylates and closes K ATP channels, and PKG promotes this inhibitory effect by preventing phosphodiesterase deactivation of PKA ( Undank et al, 2017 ). This PKA-mediated increase in insulin secretion appears contradictory to its inhibitory effect reported above; however, PKA inhibition of K ATP channels is mediated by PKG signaling, whereas leptin-PKA-AMPK signaling increases K ATP channel conductance in the absence of PKG activity ( Undank et al, 2017 ; Cochrane et al, 2020 ). PKG was also reported to inhibit insulin secretion by directly phosphorylating L-type VDCCs and decreasing [Ca 2+ ] i ; as with the effect of elevated [Ca 2+ ] i on AMPK, this might serve as a self-regulatory feedback loop ( Sandoval et al, 2017 ).…”

Section: Coordination Of Adipokinetic Hormone/glucagon and Drosophila Insulin-like Peptide/insulin Secretionmentioning

confidence: 70%

“…AMPK also inhibits insulin secretion via a leptin-mediated feedback loop ( Tsubai et al, 2016 ). In response to feeding, insulin promotes leptin secretion from adipose tissue, and leptin signaling in β cells subsequently induces protein kinase A (PKA) activation of AMPK ( Park et al, 2013 ; Cochrane et al, 2020 ). Leptin-PKA-AMPK signaling regulates membrane polarity–and thus cell excitability–by promoting K ATP channel trafficking to the β cell membrane ( Cochrane et al, 2020 ).…”

Section: Coordination Of Adipokinetic Hormone/glucagon and Drosophila Insulin-like Peptide/insulin Secretionmentioning

confidence: 99%

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The Glucagon-Like Adipokinetic Hormone in Drosophila melanogaster – Biosynthesis and Secretion

Hughson

2021

Front. Physiol.

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Metabolic homeostasis requires the precise regulation of circulating sugar titers. In mammals, homeostatic control of circulating sugar titers requires the coordinated secretion and systemic activities of glucagon and insulin. Metabolic homeostasis is similarly regulated in Drosophila melanogaster through the glucagon-like adipokinetic hormone (AKH) and the Drosophila insulin-like peptides (DILPs). In flies and mammals, glucagon and AKH are biosynthesized in and secreted from specialized endocrine cells. KATP channels borne on these cells respond to fluctuations in circulating glucose titers and thereby regulate glucagon secretion. The influence of glucagon in the pathogenesis of type 2 diabetes mellitus is now recognized, and a crucial mechanism that regulates glucagon secretion was reported nearly a decade ago. Ongoing efforts to develop D. melanogaster models for metabolic syndrome must build upon this seminal work. These efforts make a critical review of AKH physiology timely. This review focuses on AKH biosynthesis and the regulation of glucose-responsive AKH secretion through changes in CC cell electrical activity. Future directions for AKH research in flies are discussed, including the development of models for hyperglucagonemia and epigenetic inheritance of acquired metabolic traits. Many avenues of AKH physiology remain to be explored and thus present great potential for improving the utility of D. melanogaster in metabolic research.

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Section: Coordination Of Adipokinetic Hormone/glucagon and Drosophila Insulin-like Peptide/insulin Secretionmentioning

confidence: 70%

Section: Coordination Of Adipokinetic Hormone/glucagon and Drosophila Insulin-like Peptide/insulin Secretionmentioning

confidence: 99%

The Glucagon-Like Adipokinetic Hormone in Drosophila melanogaster – Biosynthesis and Secretion

Hughson

2021

Front. Physiol.

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“…For instance, leptin has been proposed to activate ATP-sensitive potassium (KATP) channels in beta cells, leading to membrane hyperpolarization and suppression of insulin release. Leptin modulates insulin secretion by promoting the translocation of KATP channels to the plasma membrane through signaling pathways, including the AMPK, PKA, and PI3K pathways [ 37 , 38 , 39 , 40 ]. Additionally, leptin increases KATP channel trafficking by inhibiting phosphatase and tensin homolog (PTEN) via glycogen synthase kinase 3β (GSK3β) [ 41 ].…”

Section: Leptinmentioning

confidence: 99%

The Interplay of Adipokines and Pancreatic Beta Cells in Metabolic Regulation and Diabetes

Kim,

Oh,

Kim

2023

Biomedicines

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The interplay between adipokines and pancreatic beta cells, often referred to as the adipo-insular axis, plays a crucial role in regulating metabolic homeostasis. Adipokines are signaling molecules secreted by adipocytes that have profound effects on several physiological processes. Adipokines such as adiponectin, leptin, resistin, and visfatin influence the function of pancreatic beta cells. The reciprocal communication between adipocytes and beta cells is remarkable. Insulin secreted by beta cells affects adipose tissue metabolism, influencing lipid storage and lipolysis. Conversely, adipokines released from adipocytes can influence beta cell function and survival. Chronic obesity and insulin resistance can lead to the release of excess fatty acids and inflammatory molecules from the adipose tissue, contributing to beta cell dysfunction and apoptosis, which are key factors in developing type 2 diabetes. Understanding the complex interplay of the adipo-insular axis provides insights into the mechanisms underlying metabolic regulation and pathogenesis of metabolic disorders. By elucidating the molecular mediators involved in this interaction, new therapeutic targets and strategies may emerge to reduce the risk and progression of diseases, such as type 2 diabetes and its associated complications. This review summarizes the interactions between adipokines and pancreatic beta cells, and their roles in the pathogenesis of diabetes and metabolic diseases.

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“…Leptin, as an essential mediator of metabolic homeostasis, regulates glucose homeostasis both externally and centrally, and the peripheral targets are pancreatic β-cells. Depending on NMDA receptors, calcium/calmodulin-dependent kinase β (CaMKKβ) and AMP-activated protein kinase (AMPK), leptin increases cell membrane protein kinase A (PKA) activity, induces ATP-sensitive potassium (K ATP ) channels transport to the β-cells surface to inhibit glucose-stimulated insulin secretion, thereby increasing K + conductance and causing β-cells hyperpolarization [ 50 ].…”

Section: The Effects Of Leptin On Epilepsymentioning

confidence: 99%

Regulatory Basis of Adipokines Leptin and Adiponectin in Epilepsy: from Signaling Pathways to Glucose Metabolism

Shan

Chen

et al. 2023

Neurochem Res

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Epilepsy is a common and severe neurological disorder in which impaired glucose metabolism leads to changes in neuronal excitability that slow or promote the development of epilepsy. Leptin and adiponectin are important mediators regulating glucose metabolism in the peripheral and central nervous systems. Many studies have reported a strong association between epilepsy and these two adipokines involved in multiple signaling cascades and glucose metabolism. Due to the complex regulatory mechanisms between them and various signal activation networks, their role in epilepsy involves many aspects, including the release of inflammatory mediators, oxidative damage, and neuronal apoptosis. This paper aims to summarize the signaling pathways involved in leptin and adiponectin and the regulation of glucose metabolism from the perspective of the pathogenesis of epilepsy. In particular, we discuss the dual effects of leptin in epilepsy and the relationship between antiepileptic drugs and changes in the levels of these two adipokines. Clinical practitioners may need to consider these factors in evaluating clinical drugs. Through this review, we can better understand the specific involvement of leptin and adiponectin in the pathogenesis of epilepsy, provide ideas for further exploration, and bring about practical significance for the treatment of epilepsy, especially for the development of personalized treatment according to individual metabolic characteristics.

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AKAP79/150 coordinates leptin-induced PKA signaling to regulate KATP channel trafficking in pancreatic β-cells

Cited by 11 publications

References 83 publications

The Glucagon-Like Adipokinetic Hormone in Drosophila melanogaster – Biosynthesis and Secretion

The Glucagon-Like Adipokinetic Hormone in Drosophila melanogaster – Biosynthesis and Secretion

The Interplay of Adipokines and Pancreatic Beta Cells in Metabolic Regulation and Diabetes

Regulatory Basis of Adipokines Leptin and Adiponectin in Epilepsy: from Signaling Pathways to Glucose Metabolism

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