AKAP 18 α and γ have opposing effects on insulin release in INS‐1E cells

Josefsen, Knud; Lee, Ying C.; Thams, Peter; Efendić, Suad; Nielsen, Jens Høiriis

doi:10.1016/j.febslet.2009.10.086

Cited by 18 publications

(15 citation statements)

References 23 publications

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“…However, recent studies link AKAP18γ to the regulation of insulin secretion in INS-1E cells. 46 AKAP18δ, which is completely conserved except for an additional 27 amino acids, is believed to localize to the inner medullary collecting duct of the kidney where it regulates Aquaporin-2 shuttling in response to vasopressin. 47 This suggests that large isoforms of AKAP18 may serve differential functions depending on the tissue type they are expressed in.…”

Section: Introductionmentioning

confidence: 99%

AKAP Phosphatase Complexes in the Heart

Redden

Dodge‐Kafka

2011

Journal of Cardiovascular Pharmacology

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Directed protein phosphorylation is indisputably critical for a multitude of cellular processes. A growing body of research demonstrates A Kinase Anchoring Proteins (AKAPs) to mediate a significant number of phosphorylation events in the heart. By acting as molecular tethers for the regulatory subunit of PKA, AKAPs focus the kinase's actions onto specific substrates. In the time since their discovery, the AKAP model has evolved in appreciation of the broader role these scaffolds play in coordinating multiple signaling enzymes in order to efficiently regulate dynamic cellular processes. The focus of this review is on the emerging role of AKAPs in regulating the three main cardiac phosphatases: Protein Phosphatase 1 by AKAP18 and Yotiao, and Protein Phosphatases 2A and 2B by mAKAP.

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Section: Introductionmentioning

confidence: 99%

AKAP Phosphatase Complexes in the Heart

Redden

Dodge‐Kafka

2011

Journal of Cardiovascular Pharmacology

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“…Although peptide disruptors for AKAP-PKA interaction have been extensively studied in research, validated small molecule disruptors suitable for therapeutic purposes are still lacking and under investigation (Troger et al 2012). Another approach to suppress AKAP-mediated signaling is small interference RNA (siRNA)-mediated knockdown of AKAP expression (Josefsen et al 2010). …”

Section: Strategies For Camp/pka Pathway Targetingmentioning

confidence: 99%

Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy

Yang

2016

Journal of Molecular Endocrinology

143

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In mammals, cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is usually elicited by binding of hormones and neurotransmitters to G protein-coupled receptors (GPCRs). cAMP exerts many of its physiological effects by activating cAMPdependent protein kinase (PKA), which in turn phosphorylates and regulates the functions of downstream protein targets including ion channels, enzymes, and transcription factors. cAMP/PKA signaling pathway regulates glucose homeostasis at multiple levels including insulin and glucagon secretion, glucose uptake, glycogen synthesis and breakdown, gluconeogenesis, and neural control of glucose homeostasis. This review summarizes recent genetic and pharmacological studies concerning the regulation of glucose homeostasis by cAMP/PKA in pancreas, liver, skeletal muscle, adipose tissues, and brain. We also discuss the strategies for targeting cAMP/PKA pathway for research and potential therapeutic treatment of type 2 diabetes mellitus (T2D).

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“…Future studies should focus on which individual Gi/Go protein isoforms inhibit which individual isoforms of the adenylyl cyclase family. More speculative would be to determine whether norepinephrine interferes in any way with the formation of multiprotein scaffolding proteins such as the A kinase anchoring proteins that play roles both upstream and downstream of cyclic AMP elevation (13,15,47,88).…”

Section: Samols Et Al (100) In 1965mentioning

confidence: 99%

Evolving insights regarding mechanisms for the inhibition of insulin release by norepinephrine and heterotrimeric G proteins

Straub

Sharp

2012

American Journal of Physiology-Cell Physiology

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Straub SG, Sharp GW. Evolving insights regarding mechanisms for the inhibition of insulin release by norepinephrine and heterotrimeric G proteins. Am J Physiol Cell Physiol 302: C1687-C1698, 2012. First published April 4, 2012 doi:10.1152/ajpcell.00282.2011.-Norepinephrine has for many years been known to have three major effects on the pancreatic ␤-cell which lead to the inhibition of insulin release. These are activation of K ϩ channels to hyperpolarize the cell and prevent the gating of voltage-dependent Ca 2ϩ channels that increase intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) and trigger release; inhibition of adenylyl cyclases, thus preventing the augmentation of stimulated insulin release by cyclic AMP; and a "distal" effect that occurs downstream of increased [Ca 2ϩ ]i to inhibit exocytosis. All three are mediated by the pertussis toxin (PTX)-sensitive heterotrimeric Gi and Go proteins. The distal inhibitory effect on exocytosis is now known to be due to the binding of G protein ␤␥ subunits to the synaptosomal-associated protein of 25 kDa (SNAP-25) on the soluble NSF attachment protein receptor (SNARE) complex. Recent studies have uncovered two more actions of norepinephrine on the ␤-cell: 1) retardation of the refilling of the readily releasable granule pool after it has been discharged, an action that is mediated by G␣i 1 and/or G␣i2; and 2) inhibition of endocytosis that is mediated by Gz. Of importance also are new findings that G␣o regulates the number of docked granules in the ␤-cell, and that G␣o 2 maintains a tonic inhibitory influence on secretion. The latter provides another explanation as to why PTX, which blocks the effect of G␣o2, was initially called "islet activating protein." Finally, there is clear evidence that overexpression of ␣ 2A-adrenergic receptors in ␤-cells can cause type 2 diabetes. pancreatic ␤-cell; K ϩ channels; adenylyl cyclases; exocytosis; granule pools; endocytosis NOREPINEPHRINE IS RESPONSIBLE for multiple effects in the body as it acts as a hormone after its release from the adrenal medulla along with epinephrine, and as a neurotransmitter when released by the central and sympathetic nervous systems. It has important functions on the cardiovascular system, on muscle, liver, and adipose tissue, and in the control of whole body metabolism. This review, however, focuses on the effects of norepinephrine on the pancreatic ␤-cell and recent advances in our knowledge. Norepinephrine has three major effects on the ␤-cell that lead to the inhibition of insulin release (65,74,102,104). It activates K ϩ channels to hyperpolarize the cell. This prevents or reverses depolarization and the consequent gating of voltage-dependent Ca 2ϩ channels that increase intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) and trigger insulin release. It inhibits adenylyl cyclases, thus preventing the augmentation of stimulated insulin release, and it has a "distal" effect that occurs downstream of increased [Ca 2ϩ

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AKAP 18 α and γ have opposing effects on insulin release in INS‐1E cells

Abstract: a b s t r a c t

Cited by 18 publications

References 23 publications

AKAP Phosphatase Complexes in the Heart

AKAP Phosphatase Complexes in the Heart

Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy

Evolving insights regarding mechanisms for the inhibition of insulin release by norepinephrine and heterotrimeric G proteins

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