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Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively reduce body weight and improve metabolic outcomes, yet established peptide-based therapies require injections and complex manufacturing. Small-molecule GLP1RAs promise oral bioavailability and scalable manufacturing, but their selective binding to human versus rodent receptors has limited mechanistic studies. The neural circuits through which these emerging therapeutics modulate feeding behavior remain undefined, particularly in comparison to established peptide-based GLP1RAs.
View Article and Find Full Text PDFBackground: Juxtaglomerular (JG) cells are sensors that control blood pressure and fluid-electrolyte homeostasis. In response to a decrease in perfusion pressure or changes in the composition and/or volume of the extracellular fluid, JG cells release renin, which initiates an enzymatic cascade that culminates in the production of angiotensin II (Ang II), a potent vasoconstrictor that restores blood pressure and fluid homeostasis. In turn, Ang II exerts a negative feedback on renin release, thus preventing excess circulating renin and the development of hypertension.
View Article and Find Full Text PDFL-type Calcium Channel Blockade Worsens Glucose Tolerance and β-Cell Function in C57BL6/J Mice Exposed to Intermittent Hypoxia.
Am J Physiol Endocrinol Metab
January 2025
Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami, Miller School of Medicine, Miami Florida.
Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated.
View Article and Find Full Text PDFComputational insights into the aggregation mechanism of human calcitonin.
Int J Biol Macromol
January 2025
School of Physical Science and Technology, Ningbo University, Ningbo 315211, China; Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, United States. Electronic address:
Human calcitonin (hCT) is a peptide hormone that regulates calcium homeostasis, but its abnormal aggregation can disrupt physiological functions and increase the risk of medullary thyroid carcinoma. To elucidate the mechanisms underlying hCT aggregation, we investigated the self-assembly dynamics of hCT segments (hCT, hCT, and hCT) and the folding and dimerization of full-length hCT through microsecond atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that hCT and hCT predominantly existed as isolated monomers with transient small-sized oligomers, indicating weak aggregation tendencies.
View Article and Find Full Text PDFInhibition of ASIC1a reduces ferroptosis in rheumatoid arthritis articular chondrocytes via the p53/NRF2/SLC7A11 pathway.
FASEB J
January 2025
School of Pharmacy, Anhui Medical University, Hefei, China.
The activation of acid-sensing ion channel 1a (ASIC1a) in response to extracellular acidification leads to an increase in extracellular calcium influx, thereby exacerbating the degeneration of articular chondrocytes in rheumatoid arthritis (RA). It has been suggested that the inhibition of extracellular calcium influx could potentially impede chondrocyte ferroptosis. The cystine transporter, solute carrier family 7 member 11 (SLC7A11), is recognized as a key regulator of ferroptosis.
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