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Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion.
J Mol Cell Biol
January 2025
Department of Endocrinology, Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of ATP-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets.
View Article and Find Full Text PDFPotential Use of GLP-1 and GIP/GLP-1 Receptor Agonists for Respiratory Disorders: Where Are We at?
Medicina (Kaunas)
December 2024
School of Medicine, PROMISE Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties, University of Palermo, 90133 Palermo, Italy.
Chronic respiratory disorders are the third leading cause of mortality globally. Consequently, there is a continuous pursuit of effective therapies beyond those currently available. The therapeutic potential of the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide/GLP-1 (GIP/GLP-1) receptor agonists extends beyond the regulation of glycemia, including glucometabolic, cardiovascular, and renal effects, rendering them viable candidates, due to their mechanisms of action, for the possible treatment of respiratory disorders.
View Article and Find Full Text PDFMaternal Low-Protein Diet During Nursing Leads to Glucose-Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats.
Biology (Basel)
December 2024
Research Group on Perinatal Programming of Metabolic Diseases: DOHaD Paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop 78556-264, Brazil.
Both perinatal malnutrition and elevated glucocorticoids are pivotal triggers of the growing global pandemic of metabolic diseases. Here, we studied the effects of metabolic stress responsiveness on glucose-insulin homeostasis and pancreatic-islet function in male Wistar offspring whose mothers underwent protein restriction during lactation. During the first two weeks after delivery, lactating dams were fed a low-protein (4% protein, LP group) or normal-protein diet (22.
View Article and Find Full Text PDFGlucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice.
JCI Insight
December 2024
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, Toronto, Canada.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived peptide hormones that potentiate glucose-dependent insulin secretion. The clinical development of GIP receptor (GIPR)-GLP-1 receptor (GLP-1R) multi-agonists exemplified by tirzepatide and emerging GIPR antagonist-GLP-1R agonist therapeutics such as maritide is increasing interest in the extra-pancreatic actions of incretin therapies. Both GLP-1 and GIP modulate inflammation, with GLP-1 also acting locally to alleviate gut inflammation in part through anti-inflammatory actions on GLP-1R+ intestinal intraepithelial lymphocytes.
View Article and Find Full Text PDF[Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity].
Rev Med Liege
December 2024
Service de Diabétologie, Nutrition et Maladies métaboliques, CHU Liège, Belgique.
Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which has been developed as once-weekly injection first for the treatment of type 2 diabetes (T2DM), then for the treatment of obesity. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. In the SURMOUNT programme, tirzepatide showed a marked reduction in body weight, never reached before with a drug, among people with obesity or overweight associated with complications linked to excess weight.
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