Antibiotic resistance is increasing among Gram-negative bacteria, prompting the development of new antibiotics as well as alternative treatment approaches. Klebsiella pneumoniae Carbapenemases (KPC) has become a major concern in the treatment of infections, since KPC-producing bacteria are resistant to a number of β -lactam and non β-lactam antibiotics in addition to hydrolyzing carbapenemases. The aim of this study is to examine the synergistic effect of human Glucose-dependent Insulinotropic Polypeptide (GIP) on KPC producer. The K. pneumoniae isolates were identified by using biochemical tests and PCR genotyping. The disc diffusion method was used to assess the antimicrobial susceptibility of each isolate, and the modified Hodge test (MHT) was used to find carbapenemases. Agar well diffusion and minimum inhibitory concentration (MIC) assays were used to validate the synergistic effect of GIP against Klebsiella species. MIC values of chosen antimicrobial compounds demonstrated a considerable synergism impact when combined with human GIP, particularly against KPC strains. The antibacterial activity of the antimicrobial compounds was boosted by 4-16 times due to human GIP, reducing the MIC values. The fractional inhibitory concentration (FIC) ranged from 0.032 to 0.25 for examined antibiotics. Thus, GIP can be considered an antibacterial adjuvant with the potential to supplement the current antibiotic spectrum.
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http://dx.doi.org/10.1016/j.micpath.2024.106823 | DOI Listing |
J Biol Chem
January 2025
Division of Experimental Animal, Hidaka Branch, Biomedical Research Center, Saitama Medical University, Saitama, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan. Electronic address:
Recent success with the use of glucagon-like peptide-1 (GLP-1) receptor analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of patients with diabetes has highlighted the role of the intestine as an endocrine organ. Gut-derived hormones, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin, have important roles in the control of energy metabolism and food intake, and are associated with the metabolic syndrome. In this study, we isolated and identified a new intestine-derived hormone, betagenin, and showed that it stimulates insulin secretion and β-cell proliferation and suppresses β-cell apoptosis.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2025
Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester, UK.
Background: Obesity is a chronic disease associated with increased risk of multiple metabolic and mental health-related comorbidities. Recent advances in obesity pharmacotherapy, particularly with glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have the potential to transform obesity and type 2 diabetes mellitus (T2DM) care by promoting marked weight loss, improving glycaemic control and addressing multiple obesity-related comorbidities, with added cardio-renal benefits. Dual agonists combining GLP-1 with other enteropancreatic hormones such as glucose-dependent insulinotropic polypeptide (GIP) have also been developed in recent years, leading to greater weight loss than using GLP-1 RAs alone.
View Article and Find Full Text PDFActa Physiol (Oxf)
February 2025
Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Background: The crucial steps in beta cell stimulus-secretion coupling upon stimulation with glucose are oscillatory changes in metabolism, membrane potential, intracellular calcium concentration, and exocytosis. The changes in membrane potential consist of bursts of spikes, with silent phases between them being dominated by membrane repolarization and absence of spikes. Assessing intra- and intercellular coupling at the multicellular level is possible with ever-increasing detail, but our current ability to simultaneously resolve spikes from many beta cells remains limited to double-impalement electrophysiological recordings.
View Article and Find Full Text PDFMol Metab
January 2025
Section of Endocrinology and Investigative Medicine, Imperial College London, United Kingdom. Electronic address:
Objectives: There is renewed interest in targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) for treatment of obesity and type 2 diabetes. G-protein coupled receptor desensitisation is suggested to reduce the long-term efficacy of glucagon-like-peptide 1 receptor (GLP-1R) agonists and may similarly affect the efficacy of GIPR agonists. We explored the extent of pancreatic GIPR functional desensitisation with sustained agonist exposure.
View Article and Find Full Text PDFCell Metab
January 2025
Departments of Cellular & Molecular Physiology and Internal Medicine (Endocrinology), Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:
Incretin receptor agonists have been effective in combatting obesity and diabetes. While the body of knowledge regarding the signaling mechanisms of glucagon-like peptide 1 (GLP-1) receptor agonists is ever-growing, glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists are less understood. The previewed papers offer insight into the impact of adipose GIPR on energy and weight homeostasis.
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