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Synthetic studies of the mutant proinsulin syndrome demonstrate correlation between folding efficiency and age of diabetes onset.
Int J Pept Res Ther
January 2025
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States 46202.
Purpose: Heterozygous mutations in the insulin gene can give rise to a monogenic diabetes syndrome due to toxic misfolding of the variant proinsulin in the endoplasmic reticulum (ER) of pancreatic β-cells. Clinical mutations are widely distributed in the sequence (86 amino acids). Misfolding induces chronic ER stress and interferes in with wildtype biosynthesis and secretion.
View Article and Find Full Text PDFSERT-Deficient Mice Fed Western Diet Reveal Altered Metabolic and Pro-Inflammatory Responses of the Liver: A Link to Abnormal Behaviors.
Front Biosci (Landmark Ed)
January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
View Article and Find Full Text PDFDoes Sex Matter in Obesity-Induced Periodontal Inflammation in the SS Mutant Rats?
Dent J (Basel)
December 2024
Oral Biology & Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA.
The incidence of obesity has dramatically increased worldwide. Obesity has been shown to exacerbate the progression of periodontal disease. Studies suggest a sex difference in periodontitis, whereby males are more sensitive to periodontal inflammation compared to females.
View Article and Find Full Text PDFCharacterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity.
bioRxiv
January 2025
Ben-May Institute for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
Insulin degrading enzyme (IDE) is a dimeric 110 kDa M16A zinc metalloprotease that degrades amyloidogenic peptides diverse in shape and sequence, including insulin, amylin, and amyloid-β, to prevent toxic amyloid fibril formation. IDE has a hollow catalytic chamber formed by four homologous subdomains organized into two ~55 kDa N- and C- domains (IDE-N and IDE-C, respectively), in which peptides bind, unfold, and are repositioned for proteolysis. IDE is known to transition between a closed state, poised for catalysis, and an open state, able to release cleavage products and bind new substrate.
View Article and Find Full Text PDFRoles of oolong tea extracts in the protection against Staphylococcus aureus infection in Caenorhabditis elegans.
J Food Sci
January 2025
Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, China.
Oolong tea, a popular traditional Chinese tea, possesses various bioactivities, but little is known about its roles in the protection against pathogens, such as Staphylococcus aureus, in vivo. This study investigated the roles of the water-soluble oolong tea extracts (OTE) on S. aureus infection in Caenorhabditis elegans, a promising model to study the host-microbe interactions in vivo.
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