Aim: To examine the effects of an enteropeptidase inhibitor, SCO-792, on kidney function in rats.
Materials And Methods: The pharmacological effects of SCO-792 were evaluated in Wistar fatty (WF) rats, a rat model of diabetic kidney disease (DKD).
Results: Oral administration of SCO-792 increased faecal protein content and improved glycaemic control in WF rats. SCO-792 elicited a rapid decrease in urine albumin-to-creatinine ratio (UACR). SCO-792 also normalized glomerular hyperfiltration and decreased fibrosis, inflammation and tubular injury markers in the kidneys. However, pioglitazone-induced glycaemic improvement had no effect on kidney variables. Dietary supplementation of amino acids (AAs), which bypass the action of enteropeptidase inhibition, mitigated the effect of SCO-792 on UACR reduction, suggesting a pivotal role for enteropeptidase. Furthermore, autophagy activity in the glomerulus, which is impaired in DKD, was elevated in SCO-792-treated rats. Finally, a therapeutically additive effect on UACR reduction was observed with a combination of SCO-792 with irbesartan, an angiotensin II receptor blocker.
Conclusions: This study is the first to demonstrate that enteropeptidase inhibition is effective in improving disease conditions in DKD. SCO-792-induced therapeutic efficacy is likely to be independent of glycaemic control and mediated by the regulation of AAs and autophagy. Taken together with a combination effect of irbesartan, SCO-792 may be a novel therapeutic option for patients with DKD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756647 | PMC |
| http://dx.doi.org/10.1111/dom.14190 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metformin inhibits digestive proteases and impairs protein digestion in mice.
J Biol Chem
December 2023
Microbial Sciences Institute, Yale University, West Haven, Connecticut, USA; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:
Metformin is among the most prescribed medications worldwide and the first-line therapy for type 2 diabetes. However, gastrointestinal side effects are common and can be dose limiting. The total daily metformin dose frequently reaches several grams, and poor absorption results in high intestinal drug concentrations.
View Article and Find Full Text PDFMicrobial dietary protein metabolism regulates GLP-1 mediated intestinal transit.
FASEB J
October 2023
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Depletion of gut microbiota is associated with inefficient energy extraction and reduced production of short-chain fatty acids from dietary fibers, which regulates colonic proglucagon (Gcg) expression and small intestinal transit in mice. However, the mechanism by which the gut microbiota influences dietary protein metabolism and its corresponding effect on the host physiology is poorly understood. Enteropeptidase inhibitors block host protein digestion and reduce body weight gain in diet-induced obese rats and mice, and therefore they constitute a new class of drugs for targeting metabolic diseases.
View Article and Find Full Text PDFCharacterization of digestive proteases in the gut of a basal deuterostome.
J Exp Biol
August 2023
Zoological Institute, Christian-Albrechts University of Kiel, 24118 Kiel, Germany.
Digestive systems are complex organs that allow organisms to absorb energy from their environment to fuel vital processes such as growth, development and the maintenance of homeostasis. A comprehensive understanding of digestive physiology is therefore essential to fully understand the energetics of an organism. The digestion of proteins is of particular importance because most heterotrophic organisms are not able to synthesize all essential amino acids.
View Article and Find Full Text PDFEfficient production of fluorophore-labeled CC chemokines for biophysical studies using recombinant enterokinase and recombinant sortase.
Biopolymers
March 2024
Molecular Cell Biology, Health Sciences Research Institute, University of California Merced, Merced, California, USA.
Article Synopsis
- Chemokines are crucial proteins in the immune system that help regulate inflammation by attracting leukocytes; targeting and inhibiting them is a key anti-inflammatory strategy.
- The study describes a method for producing fluorescently labeled chemokines using recombinant DNA techniques and custom enzymes, which is cost-effective compared to commercial reagents.
- The resulting fluorescent chemokine (vMIP-fluor) was successfully used in binding studies, showcasing its potential in anti-inflammatory therapies and demonstrating its effectiveness in competition assays with other chemokines.
An Exploratory Randomized Trial of SCO-792, an Enteropeptidase Inhibitor, in Patients With Type 2 Diabetes and Albuminuria.
Kidney Int Rep
January 2023
Drug Discovery Laboratories, SCOHIA PHARMA, Inc., Kanagawa, Japan.
Introduction: Elevated plasma amino acid levels overload kidney function by increasing glomerular filtration rate (GFR). Inhibiting gut amino acid intake may have therapeutic benefits for patients with kidney dysfunction. For a prospective phase 2a trial, we carried out an exploratory evaluation of the safety and efficacy of SCO-792, an enteropeptidase inhibitor that blocks gut amino acid intake, in patients with type 2 diabetes mellitus (T2DM) and albuminuria.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!