Exendin

OBJECTIVES: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro . Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo ...

OBJECTIVE: Combination therapies with gut hormone analogues represent promising treatment strategies for obesity. This pilot study investigates the therapeutic potential of modulators of the glucagon-like peptide 1 (GLP-1) and neuropeptide Y (NPY) system using GLP-1 receptor agonists (semaglutide) and antagonists (exendin(9-39)), as well as non-selective and NPY-Y2-receptor selective peptide tyrosine tyrosine (PYY) analogues (PYY3-36/NNC0165-0020 and NNC0165-1273) and an NPY-Y2 receptor antagonist (JNJ 31020028)...

AIM: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects. METHODS: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0...

OBJECTIVE: Lipotoxic injury from renal lipid accumulation in obesity and type 2 diabetes (T2D) is implicated in associated kidney damage. However, models examining effects of renal ectopic lipid accumulation independent of obesity or T2D are lacking. We generated renal tubule-specific adipose triglyceride lipase knockout (RT-SAKO) mice to determine if this targeted triacylglycerol (TAG) over-storage affects glycemic control and kidney health. METHODS: Male and female RT-SAKO mice and their control littermates were tested for changes in glycemic control at 10-12 and 16-18 weeks of age...

BACKGROUND: Despite the strong evidence concerning carcinogenic roles of glucagon-like peptide 1 receptor (GLP1R), the role of this gene in endometrial cancer (EC) remains elusive. This study investigated the properties of GLP1R on EC in vitro . METHODS: The expression of GLP1R in EC was detected by RT-qPCR, immunohistochemistry, and western blotting. Cell viability, cell cycle, apoptosis, migration, invasion and ferroptosis were assessed through CCK-8, flow cytometry, wound healing, transwell, DCFH-DA and western blotting, respectively...

BACKGROUND: The beneficial role of glucose-dependent insulinotropic polypeptide receptor (GIPR) in weight control and maintaining glucose levels has led to the development of several multi-agonistic peptide drug candidates, targeting GIPR and glucagon like peptide 1 receptor (GLP1R) and/or the glucagon receptor (GCGR). The in vivo quantification of target occupancy by these drugs would accelerate the development of new drug candidates. The aim of this study was to evaluate a novel peptide (GIP1234), based on previously reported ligand DOTA-GIP-C803, modified with a fatty acid moiety to prolong its blood circulation...

Neurodegenerative disorders, which affect millions worldwide, are marked by a steady decline of neurons that are selectively susceptible. Due to the complex pathological processes underlying neurodegeneration, at present, there is no viable therapy available for neurodegenerative disorders. Consequently, the establishment of a novel therapeutic approach for such conditions is a clinical void that remains. The potential significance of various peptides as neuroprotective interventions for neurodegenerative disorders is gaining increasing attention...

BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the E×4formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified E×4(Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection. METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process...

A case of recurrent insulinoma spanning 4 decades is described. Following a delayed diagnosis, hyperinsulinemic hypoglycemia was confirmed in a 24-year-old woman during early pregnancy. Initial surgery, culminating in subtotal pancreatectomy, was noncurative. A 1-cm insulinoma was subsequently resected from the head of the pancreas postpartum, with postoperative resolution of hypoglycemia. However, 32 years later, the patient experienced a recurrence of hypoglycemic symptoms. Eventually, a subcentimeter extrapancreatic lesion was identified anterior to the pancreatic head on gallium-68 DOTA-Exendin-4 positron emission tomography/computed tomography...

Nonunions and delayed unions pose significant challenges in orthopedic treatment, with current therapies often proving inadequate. Bone tissue engineering (BTE), particularly through endochondral ossification (ECO), emerges as a promising strategy for addressing critical bone defects. This study introduces mesenchymal stem cells overexpressing Exendin-4 (MSC-E4), designed to modulate bone remodeling via their autocrine and paracrine functions. We established a type I collagen (Col-I) sponge-based in vitro model that effectively recapitulates the ECO pathway...

BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system. METHODS: To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide...

Delirium is the most common neurological complication after cardiac surgery with adverse impacts on surgical outcomes. Advanced age is an independent risk factor for delirium occurrence but its underlying mechanisms are not fully understood. Although increased A1 astrocytes and abnormal hippocampal networks are involved in neurodegenerative diseases, whether A1 astrocytes and hippocampal network changes are involved in the delirium-like behavior of aged mice remains unknown. In the present study, a mice model of myocardial ischemia-reperfusion mimicking cardiac surgery and various assessments were used to investigate the different susceptibility of the occurrence of delirium-like behavior between young and aged mice and the underlying mechanisms...

AIM: Bile acid sequestrants are cholesterol-lowering drugs, which also improve glycaemic control in people with type 2 diabetes. The mechanism behind the glucose-lowering effect is unknown but has been proposed to be mediated by increased glucagon-like peptide-1 (GLP-1) secretion. Here, we investigated the glucose-lowering effects of sevelamer including any contribution from GLP-1 in people with type 2 diabetes. MATERIALS AND METHODS: In a randomized, double-blind, placebo-controlled, crossover study, 15 people with type 2 diabetes on metformin monotherapy underwent two 17-day treatment periods with the bile acid sequestrant sevelamer and placebo, respectively, in a randomized order and with an interposed wash-out period of minimum 6 weeks...

Feline diabetes mellitus is a common endocrine disease with increasing prevalence. It shows similarities with human type 2 diabetes and is characterized by insulin resistance and deficient insulin secretion. Moreover, cats and humans belong to the very few species that form amyloid depositions in the pancreatic islets. However, little is known about cat islet function and no studies have addressed insulin secretion from isolated islets ex vivo. The aim of this study was to establish a protocol for isolation of islets of Langerhans from pancreata of cats euthanized due to disease, and to evaluate insulin secretion responses to various physiological and pharmacological stimuli...

Glucagon-like peptide-1 (GLP-1) receptor agonists are used in diabetes management and can have a potential application in cancer therapy. While their involvement in cancer treatment is still being studied, recent research suggests they may have benefits in cancer therapy. A comprehensive literature search was conducted using search engines like Google Scholar, Scopus, and PubMed to explore the effects of GLP-1 receptor agonists in tumor suppression and regression. Mostly in-vitro studies on GLP-1 receptor agonists have shown promising effects in inhibiting cancer cell growth, inducing apoptosis, and modulating angiogenesis and have been reported to be beneficial in colon, prostate, gall bladder, ovarian, and endometrial carcinomas...

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a metabolic, endocrine hormone regulating insulin sensitivity, energy expenditure, and lipid metabolism. It has significant potential as a therapeutic drug for treating type 2 diabetes and obesity. However, the clinical efficacy of FGF21 analogs is limited due to their instability and short half-life. Glucagon-like peptide 1 (GLP-1) receptor agonists have been recognized as effective medications for type 2 diabetes mellitus and obesity over the past two decades...

High plasma concentrations of insulin can cause acute laminitis. Ponies and horses with insulin dysregulation (ID) exhibit marked hyperinsulinaemia in response to dietary hydrolysable carbohydrates. Glucagon-like peptide-1 (GLP-1), an incretin hormone released from the gastrointestinal tract, enhances insulin release, and is increased post-prandially in ponies with ID. The aim of this study was to determine whether blocking the GLP-1 receptor reduces the insulin response to a high glycaemic meal. Five adult ponies were adapted to a cereal meal then given two feed challenges 24 h apart of a meal containing 3 g/kg BW micronized maize...

High-sugar and high-fat diets cause significant harm to health, especially via metabolic diseases. In this study, the protective effects of the antidiabetic drug exenatide (synthetic exendin-4), a glucagon-like peptide 1 (GLP-1) receptor agonist, on high-fat and high-glucose (HFHG)-induced renal injuries were investigated in vivo and in vitro. In vivo and in vitro renal injury models were established. Metabolomic analysis based on 1 H-nuclear magnetic resonance was performed to examine whether exenatide treatment exerts a protective effect against kidney injury in diabetic rats and to explore its potential molecular mechanism...

OBJECTIVES: The protection of spiral ganglion neurons (SGNs) is crucial for hearing loss. Exendin-4 has been shown to have neuroprotective effects in several neurological disorders. Therefore, this study aimed to investigate the effect of the glucagon-like protein-1 receptor (GLP-1R) agonist exendin-4 on kanamycin-induced injury in mouse SGNs in vitro . MATERIALS AND METHODS: In this study, GLP-1R expression in SGNs was verified by immunofluorescence and immunohistochemical staining...

Septic encephalopathy (SE) is a critical mental status allied with potential long-term cognitive deficits and higher mortality rates in ICU patients. The shortfall in comprehending its pathophysiology limits effective treatment options, however, GLP-1 agonists opened an entry point for future neurodegenerative disease management. This work aims to validate mTORC1 prospective role in the pathogenesis of SE using rapamycin (RAPA) and investigate the involvement of this complex in exendin-4 (EX4) neurotherapeutic potential using cecal ligation and puncturing (CLP)-induced SE model, focusing on necroptosis as a novel intervention besides necrosis and apoptosis...