scholarly journals Norepinephrine Regulation of Ventromedial Hypothalamic Nucleus Metabolic-Sensory Neuron 5′-AMP-Activated Protein Kinase Activity: Impact of Estradiol

2020 ◽  
Vol 21 (6) ◽  
pp. 2013
Author(s):  
A. S. M. Hasan Mahmood ◽  
Md. Main Uddin ◽  
Mostafa M. H. Ibrahim ◽  
Karen P. Briski
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Hypothalamic Nucleus ◽  
Current Evidence ◽  
Protein Kinase Activity ◽  
Ventromedial Hypothalamic Nucleus ◽  
Glucose Dysregulation ◽  
Endogenous Estrogen ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The mediobasal hypothalamus (MBH) shapes the neural regulation of glucostasis by 5′-AMP-activated protein kinase (AMPK)-dependent mechanisms. Yet, the neurochemical identity and neuroanatomical distribution of MBH neurons that express glucoprivic-sensitive AMPK remain unclear. The neurotransmitters γ-aminobutyric acid (GABA) and nitric oxide (NO) act within the MBH to correspondingly inhibit or stimulate glucose counter-regulation. The current review highlights recent findings that GABA and NO, neurons located in the ventromedial hypothalamic nucleus (VMN), a distinct important element of the MBH, are direct targets of noradrenergic regulatory signaling, and thereby, likely operate under the control of hindbrain metabolic-sensory neurons. The ovarian hormone estradiol acts within the VMN to govern energy homeostasis. Discussed here is current evidence that estradiol regulates GABA and NO nerve cell receptivity to norepinephrine and moreover, controls the noradrenergic regulation of AMPK activity in each cell type. Future gains in insight on mechanisms underpinning estradiol’s impact on neurotransmitter communication between the hindbrain and hypothalamic AMPKergic neurons are expected to disclose viable new molecular targets for the therapeutic simulation of hormonal enhancement of neuro-metabolic stability during circumstances of diminished endogenous estrogen secretion or glucose dysregulation.

scholarly journals Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin

2007 ◽  
Vol 192 (3) ◽  
pp. 605-614 ◽  
Author(s):  
Fang Cai ◽  
Armen V Gyulkhandanyan ◽  
Michael B Wheeler ◽  
Denise D Belsham
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Cell Model ◽  
Neuronal Cell ◽  
Cell Types ◽  
Glucose Sensing ◽  
Protein Kinase Activity ◽  
Energy Status ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.

scholarly journals Ventrolateral ventromedial hypothalamic nucleus GABA neuron adaptation to recurring Hypoglycemia correlates with up-regulated 5′-AMP-activated protein kinase activity

2021 ◽  
Vol 8 (4) ◽  
pp. 510-525
Author(s):  
Abdulrahman Alhamyani ◽  
◽  
Prabhat R Napit ◽  
Haider Ali ◽  
Mostafa MH Ibrahim ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucocorticoid Receptors ◽  
Negative Energy ◽  
Hypothalamic Nucleus ◽  
Protein Kinase Activity ◽  
Gamma Aminobutyric Acid ◽  
Gaba Neurons ◽  
Ventromedial Hypothalamic Nucleus ◽  
Acute Hypoglycemia ◽  
Amp Activated Protein Kinase

<abstract> <p>Gamma-aminobutyric acid (GABA) acts on ventromedial hypothalamic targets to suppress counter-regulatory hormone release, thereby lowering blood glucose. Maladaptive up-regulation of GABA signaling is implicated in impaired counter-regulatory outflow during recurring insulin-induced hypoglycemia (RIIH). Ventromedial hypothalamic nucleus (VMN) GABAergic neurons express the sensitive energy gauge 5′-AMP-activated protein kinase (AMPK). Current research used high-neuroanatomical resolution single-cell microdissection tools to address the premise that GABAergic cells in the VMNvl, the primary location of ‘glucose-excited’ metabolic-sensory neurons in the VMN, exhibit attenuated sensor activation during RIIH. Data show that during acute hypoglycemia, VMNvl glutamate decarboxylase<sub>65/67</sub> (GAD)-immunoreactive neurons maintain energy stability, yet a regional subset of this population exhibited decreased GAD content. GABA neurons located along the rostrocaudal length of the VMNvl acclimated to RIIH through a shift to negative energy imbalance, e.g. increased phosphoAMPK expression, alongside amplification/gain of inhibition of GAD profiles. Acquisition of negative GAD sensitivity may involve altered cellular receptivity to noradrenergic input via α<sub>2</sub>-AR and/or β<sub>1</sub>-AR. Suppression of VMNvl GABA nerve cell signaling during RIIH may differentiate this neuroanatomical population from other, possibly non-metabolic-sensory GABA neurons in the MBH. Data here also provide novel evidence that VMNvl GABA neurons are direct targets of glucocorticoid control, and show that glucocorticoid receptors may inhibit RIIH-associated GAD expression in rostral VMNvl GABAergic cells through AMPK-independent mechanisms.</p> </abstract>

scholarly journals Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

2007 ◽  
Vol 403 (3) ◽  
pp. 473-481 ◽  
Author(s):  
Ho-Jin Koh ◽  
Michael F. Hirshman ◽  
Huamei He ◽  
Yangfeng Li ◽  
Yasuko Manabe ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Activity ◽  
Chronic Exercise ◽  
Rat Adipocytes ◽  
Compound C ◽  
Isolated Adipocytes ◽  
Ampk Activity ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase

Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKα1 and α2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the β-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKα1 and α2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKα1 and α2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis.

Hypoxia and AMP independently regulate AMP-activated protein kinase activity in heart

2005 ◽  
Vol 288 (5) ◽  
pp. H2412-H2421 ◽  
Author(s):  
Markus Frederich ◽  
Li Zhang ◽  
James A. Balschi
Keyword(s):  
Protein Kinase ◽  
Metabolic Inhibitors ◽  
Protein Kinase Activity ◽  
Α Subunit ◽  
Rat Hearts ◽  
Upstream Kinase ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The hypothesis was tested that hypoxia increases AMP-activated protein kinase (AMPK) activity independently of AMP concentration ([AMP]) in heart. In isolated perfused rat hearts, cytosolic [AMP] was changed from 0.2 to 16 μM using metabolic inhibitors during both normal oxygenation (95% O2-5% CO2, normoxia) and limited oxygenation (95% N2-5% CO2, hypoxia). Total AMPK activity measured in vitro ranged from 2 to 40 pmol·min−1·mg protein−1 in normoxic hearts and from 5 to 55 pmol·min−1·mg protein−1 in hypoxic hearts. The dependence of the in vitro total AMPK activity on the in vivo cytosolic [AMP] was determined by fitting the measurements from individual hearts to a hyperbolic equation. The [AMP] resulting in half-maximal total AMPK activity ( A0.5) was 3 ± 1 μM for hypoxic hearts and 28 ± 13 μM for normoxic hearts. The A0.5 for α2-isoform AMPK activity was 2 ± 1 μM for hypoxic hearts and 13 ± 8 μM for normoxic hearts. Total AMPK activity correlated with the phosphorylation of the Thr172 residue of the AMPK α-subunit. In potassium-arrested hearts perfused with variable O2 content, α-subunit Thr172 phosphorylation increased at O2 ≤ 21% even though [AMP] was <0.3 μM. Thus hypoxia or O2 ≤ 21% increased AMPK phosphorylation and activity independently of cytosolic [AMP]. The hypoxic increase in AMPK activity may result from either direct phosphorylation of Thr172 by an upstream kinase or reduction in the A0.5 for [AMP].

scholarly journals AMP-activated protein kinase pathway and bone metabolism

2011 ◽  
Vol 212 (3) ◽  
pp. 277-290 ◽  
Author(s):  
J Jeyabalan ◽  
M Shah ◽  
B Viollet ◽  
C Chenu
Keyword(s):  
Protein Kinase ◽  
Energy Homeostasis ◽  
Bone Cells ◽  
Peripheral Tissues ◽  
Ampk Signaling ◽  
Obesity And Diabetes ◽  
Regulate Food Intake ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

There is increasing evidence that osteoporosis, similarly to obesity and diabetes, could be another disorder of energy metabolism. AMP-activated protein kinase (AMPK) has emerged over the last decade as a key sensing mechanism in the regulation of cellular energy homeostasis and is an essential mediator of the central and peripheral effects of many hormones on the metabolism of appetite, fat and glucose. Novel work demonstrates that the AMPK signaling pathway also plays a role in bone physiology. Activation of AMPK promotes bone formationin vitroand the deletion of α or β subunit of AMPK decreases bone mass in mice. Furthermore, AMPK activity in bone cells is regulated by the same hormones that regulate food intake and energy expenditure through AMPK activation in the brain and peripheral tissues. AMPK is also activated by antidiabetic drugs such as metformin and thiazolidinediones (TZDs), which also impact on skeletal metabolism. Interestingly, TZDs have detrimental skeletal side effects, causing bone loss and increasing the risk of fractures, although the role of AMPK mediation is still unclear. These data are presented in this review that also discusses the potential roles of AMPK in bone as well as the possibility for AMPK to be a future therapeutic target for intervention in osteoporosis.

scholarly journals Dissecting the Role of 5′-AMP for Allosteric Stimulation, Activation, and Deactivation of AMP-activated Protein Kinase

2006 ◽  
Vol 281 (43) ◽  
pp. 32207-32216 ◽  
Author(s):  
Marianne Suter ◽  
Uwe Riek ◽  
Roland Tuerk ◽  
Uwe Schlattner ◽  
Theo Wallimann ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Phosphatase ◽  
Energy Homeostasis ◽  
Adenine Nucleotides ◽  
Enzyme Preparations ◽  
Activity Measurements ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is a heterotrimeric protein kinase that is crucial for cellular energy homeostasis of eukaryotic cells and organisms. Here we report on the activation of AMPK α1β1γ1 and α2β2γ1 by their upstream kinases (Ca2+/calmodulin-dependent protein kinase kinase-β and LKB1-MO25α-STRADα), the deactivation by protein phosphatase 2Cα, and on the extent of stimulation of AMPK by its allosteric activator AMP, using purified recombinant enzyme preparations. An accurate high pressure liquid chromatography-based method for AMPK activity measurements was established, which allowed for direct quantitation of the unphosphorylated and phosphorylated artificial peptide substrate, as well as the adenine nucleotides. Our results show a 1000-fold activation of AMPK by the combined effects of upstream kinase and saturating concentrations of AMP. The two AMPK isoforms exhibit similar specific activities (6 μmol/min/mg) and do not differ significantly by their responsiveness to AMP. Due to the inherent instability of ATP and ADP, it proved impossible to assay AMPK activity in the absolute absence of AMP. However, the half-maximal stimulatory effect of AMP is reached below 2 μm. AMP does not appear to augment phosphorylation by upstream kinases in the purified in vitro system, but deactivation by dephosphorylation of AMPK α-subunits at Thr-172 by protein phosphatase 2Cα is attenuated by AMP. Furthermore, it is shown that neither purified NAD+ nor NADH alters the activity of AMPK in a concentration range of 0–300 μm, respectively. Finally, evidence is provided that ZMP, a compound formed in 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside-treated cells to activate AMPK in vivo, allosterically activates purified AMPK in vitro, but compared with AMP, maximal activity is not reached. These data shed new light on physiologically important aspects of AMPK regulation.

scholarly journals Acute regulation of 5′-AMP-activated protein kinase by long-chain fatty acid, glucose and insulin in rat primary adipocytes

2012 ◽  
Vol 33 (1) ◽  
Author(s):  
Abdel Hebbachi ◽  
David Saggerson
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Hormone Sensitive Lipase ◽  
Protein Kinase Activity ◽  
Compound C ◽  
Hormone Sensitive ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Acid Esterification ◽  
Long Chain

Palmitate increased AMPK (5′-AMP-activated protein kinase) activity, glucose utilization and 2-DOG (2-deoxyglucose) transport in rat adipocytes. All three effects were blocked by the AMPK inhibitor Compound C, leading to the conclusion that in response to an increase in long-chain NEFA (non-esterified fatty acid) concentration AMPK mediated an enhancement of adipocyte glucose transport, thereby providing increased glycerol 3-phosphate for FA (fatty acid) esterification to TAG (triacylglycerol). Activation of AMPK in response to palmitate was not due to an increase in the adipocyte AMP:ATP ratio. Glucose decreased AMPK activity and effects of palmitate and glucose on AMPK activity were antagonistic. While insulin had no effect on basal AMPK activity insulin did decrease AMPK activity in the presence of palmitate and also decreased the percentage effectiveness of palmitate to increase the transport of 2-DOG. It is suggested that activation of adipocyte AMPK by NEFA, as well as decreasing the activity of hormone-sensitive lipase, could modulate adipose tissue dynamics by increasing FA esterification and, under certain circumstances, FA synthesis.

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