Physiological Temperature Changes Fine-Tune β2- Adrenergic Receptor-Induced Cytosolic cAMP Accumulation

Faro, Dennis; Boekhoff, Ingrid; Gudermann, Thomas; Breit, Andreas

doi:10.1124/molpharm.121.000309

Cited by 2 publications

(3 citation statements)

References 34 publications

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“…In order to determine the effects of glucose on cAMP levels, we incubated cells for 24 h either with 0.1 or with 2.5 mM glucose in the presence of [ 3 H]-adenine and measured basal, noradrenalin (NA)-, and forskolin (FSK)-induced cAMP accumulation afterwards. NA activates β 2 - and β 3 -AR in mHypoA-2/10 cells, and FSK is a direct activator of AC [ 41 ]. Using sequential chromatography, we first tested whether glucose would affect the conversion of [ 3 H]-adenine to [ 3 H]-ATP.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, in contrast to NA, pertussis toxin treatment affected FSK-induced cAMP accumulation (data not shown), suggesting that the involvement of G i proteins in ligand-induced cAMP accumulation contributes to the glucose effect on this process. However, NA is a key activator of the HPT axes because it induces thyreoliberin release from the hypothalamus via cAMP production [ 22 , 41 ]. Thus, it is reasonable to assume that glucose-induced enhancement of NA signaling might activate the HPT axis and thus enhance metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…mHypoA-2/10 express a wide array of hypothalamic markers [ 38 ]. We have recently reported that these cells behave similar to thyreoliberin -positive neurons of the paraventricular nucleus and that they respond to a wide range of hormones such as melanocortins, serotonin, catecholamines, and IGF [ 20 , 37 , 39 , 40 , 41 ]. GT1-7 cells were kindly provided from Dr. Weiner (University of California, San Francisco, CA, USA) and behave like GnRH-secreting cells of the hypothalamus [ 42 , 43 ].…”

Section: Methodsmentioning

confidence: 99%

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Analysis of the Glucose-Dependent Transcriptome in Murine Hypothalamic Cells

Webert¹,

Faro²,

Zeitlmayr³

et al. 2022

Cells

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Glucose provides vital energy for cells and contributes to gene expression. The hypothalamus is key for metabolic homeostasis, but effects of glucose on hypothalamic gene expression have not yet been investigated in detail. Thus, herein, we monitored the glucose-dependent transcriptome in murine hypothalamic mHypoA-2/10 cells by total RNA-seq analysis. A total of 831 genes were up- and 1390 genes were downregulated by at least 50%. Key genes involved in the cholesterol biosynthesis pathway were upregulated, and total cellular cholesterol levels were significantly increased by glucose. Analysis of single genes involved in fundamental cellular signaling processes also suggested a significant impact of glucose. Thus, we chose ≈100 genes involved in signaling and validated the effects of glucose on mRNA levels by qRT-PCR. We identified Gnai1–3, Adyc6, Irs1, Igfr1, Hras, and Elk3 as new glucose-dependent genes. In line with this, cAMP measurements revealed enhanced noradrenalin-induced cAMP levels, and reporter gene assays elevated activity of the insulin-like growth factor at higher glucose levels. Key data of our studies were confirmed in a second hypothalamic cell line. Thus, our findings link extra cellular glucose levels with hypothalamic lipid synthesis and pivotal intracellular signaling processes, which might be of particular interest in situations of continuously increased glucose levels.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%