Pancreatic regulation of glucose homeostasis

Experimental & Molecular Medicine, Journal Year: 2016, Volume and Issue: 48(3), P. e219 - e219

Published: March 11, 2016

In order to ensure normal body function, the human is dependent on a tight control of its blood glucose levels. This accomplished by highly sophisticated network various hormones and neuropeptides released mainly from brain, pancreas, liver, intestine as well adipose muscle tissue. Within this network, pancreas represents key player secreting sugar-lowering hormone insulin opponent glucagon. However, disturbances in interplay peptides involved may lead metabolic disorders such type 2 diabetes mellitus (T2DM) whose prevalence, comorbidities medical costs take dramatic scale. Therefore, it utmost importance uncover understand mechanisms underlying interactions improve existing anti-diabetic therapies drugs one hand develop new therapeutic approaches other. review summarizes with other organs tissues that maintain homeostasis. Furthermore, their impact signaling pathways will be discussed. Recent advances our understanding how pancreatic cells respond raise possibility treatments for diabetes. The plays role sugar levels through release glucagon insulin, which oppose balance another. Weiping Han, Pia V. Röder colleagues at Agency Science, Technology Research Singapore have reviewed recent studies reveal complex between including gut, These identify many external triggers internal events follow exposure. Targeting some these newly identified molecules, enzymes underlie secretion likely yield

Language: Английский

---

Relaxin Family Peptides and Their Receptors

Physiological Reviews, Journal Year: 2013, Volume and Issue: 93(1), P. 405 - 480

Published: Jan. 1, 2013

There are seven relaxin family peptides that all structurally related to insulin. Relaxin has many roles in female and male reproduction, as a neuropeptide the central nervous system, vasodilator cardiac stimulant cardiovascular an antifibrotic agent. Insulin-like peptide-3 (INSL3) clearly defined specialist relaxin-3 is primarily involved stress metabolic control, INSL5 widely distributed particularly gastrointestinal tract. Although they insulin, produce their physiological effects by activating group of four G protein-coupled receptors (GPCRs), peptide 1–4 (RXFP1–4). INSL3 cognate ligands for RXFP1 RXFP2, respectively, leucine-rich repeat containing GPCRs. activates wide spectrum signaling pathways generate second messengers include cAMP nitric oxide, whereas RXFP2 subset these pathways. Relaxin-3 RXFP3 RXFP4 closely small when activated inhibit production activate MAP kinases. there still unanswered questions regarding mode action peptides, it clear have important could be exploited therapeutic benefit.

Language: Английский

---

Establishing and regulating the composition of cilia for signal transduction

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(7), P. 389 - 405

Published: April 4, 2019

Language: Английский

---

Proteomics of Primary Cilia by Proximity Labeling

Developmental Cell, Journal Year: 2015, Volume and Issue: 35(4), P. 497 - 512

Published: Nov. 1, 2015

Language: Английский

---

International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases

Pharmacological Reviews, Journal Year: 2017, Volume and Issue: 69(2), P. 93 - 139

Published: March 2, 2017

Adenylyl cyclases (ACs) generate the second messenger cAMP from ATP. Mammalian cells express nine transmembrane AC (mAC) isoforms (AC1–9) and a soluble (sAC, also referred to as AC10). This review will largely focus on mACs. mACs are activated by G-protein Gα_s regulated multiple mechanisms. differentially expressed in tissues regulate numerous diverse cell functions. localize distinct membrane compartments form signaling complexes. sAC is bicarbonate with physiologic roles first described testis. Crystal structures of catalytic core hybrid mAC available. These provide detailed insights into mechanism constitute basis for development isoform-selective activators inhibitors. Although potent competitive noncompetitive inhibitors available, it challenging obtain compounds high isoform selectivity due conservation core. Accordingly, caution must be exerted interpretation intact-cell studies. The activators, plant diterpene forskolin being starting compound, has been equally challenging. There no known endogenous ligand binding site. Recently, selective was reported. An emerging field association gene polymorphisms human diseases. For example, mutations AC5 (ADCY5) cause hyperkinetic extrapyramidal motor disorders. Overall, contrast guanylyl cyclase field, our understanding (patho)physiology clinically useful drugs targeting ACs still its infancy.

Language: Английский

---

Emerging Role of cAMP/AMPK Signaling

Cells, Journal Year: 2022, Volume and Issue: 11(2), P. 308 - 308

Published: Jan. 17, 2022

The 5′-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a natural energy sensor in mammalian cells that plays key role cellular and systemic homeostasis. At the level, AMPK supports numerous processes required for redox homeostasis, including mitochondrial biogenesis, autophagy, glucose lipid metabolism. Thus, understanding pathways regulating activity crucial developing strategies to treat metabolic disorders. Mounting evidence suggests presence of link between cyclic AMP (cAMP) signaling. cAMP signaling known be activated circumstances physiological stress due release hormones, such as adrenaline glucagon, which followed by activation membrane-bound adenylyl cyclase elevation cAMP. Because majority stresses are associated with elevated consumption, it not surprising may promote activity. Aside from cAMP/AMPK axis, reports have suggested its several pathologies, inflammation, ischemia, diabetes, obesity, aging. Furthermore, novel provided more mechanistic insight into regulation axis. In particular, distinct microdomains generated soluble basal induced has recently been demonstrated. present review, we discuss current advances axis homeostasis explore some translational aspects.

Language: Английский

---

Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR

Science, Journal Year: 2023, Volume and Issue: 379(6639), P. 1352 - 1358

Published: March 31, 2023

Glycine is a major neurotransmitter involved in several fundamental neuronal processes. The identity of the metabotropic receptor mediating slow neuromodulatory effects glycine unknown. We identified an orphan G protein–coupled receptor, GPR158, as (mGlyR). and related modulator, taurine, directly bind to Cache domain this event inhibits activity intracellular signaling complex regulator protein 7–G β5 (RGS7-Gβ5), which associated with receptor. signals through mGlyR inhibit production second messenger adenosine 3′,5′-monophosphate. further show that glycine, but not acts regulate excitability cortical neurons. These results identify system implications for understanding cognition affective states.

Language: Английский

---

Direct interrogation of context-dependent GPCR activity with a universal biosensor platform

Cell, Journal Year: 2024, Volume and Issue: 187(6), P. 1527 - 1546.e25

Published: Feb. 26, 2024

Language: Английский

---

Adenylyl Cyclase–A-kinase Anchoring Protein Complexes: The Next Dimension in cAMP Signaling

Molecular Pharmacology, Journal Year: 2009, Volume and Issue: 76(5), P. 935 - 941

Published: Aug. 14, 2009

The formation of multiprotein complexes is a repeated theme in biology ranging from the regulation extracellular signal-regulated kinase and cAMP signaling pathways to postsynaptic density or tight junctions. A-kinase anchoring proteins (AKAPs) are well known for their ability scaffold protein A components upstream downstream production, including G protein-coupled receptors, cAMP-dependent Rap-exchange factors, phosphodiesterases. Specific adenylyl cyclase (AC) isoforms have also been identified as AKAP complexes, namely AKAP79, Yotiao, mAKAP. In this review, we summarize recent evidence AC-AKAP requirements compartmentalization signaling. AKAPs assemble intricate feedback loops control spatiotemporal aspects adds yet another dimension classic pathway.

Language: Английский

---

Regulation by Ca2+-Signaling Pathways of Adenylyl Cyclases

Cold Spring Harbor Perspectives in Biology, Journal Year: 2010, Volume and Issue: 3(1), P. a004143 - a004143

Published: Dec. 1, 2010

Michelle L. Halls and Dermot M.F. Cooper Department of Pharmacology, University Cambridge, CB2 1PD, United Kingdom Correspondence: dmfc2{at}cam.ac.uk

Language: Английский

---