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https://www.readbyqxmd.com/read/29662318/rare-malignant-insulinoma-with-multiple-liver-metastases-derived-from-ectopic-pancreas-3-year-follow-up-and-literature-review
#1
Qing Liu, Jianghui Duan, Yumin Zheng, Jie Luo, Xiaopin Cai, Huangying Tan
Here, we report the diagnosis and treatment of a very rare case of malignant insulinoma derived from ectopic pancreas. A middle-aged woman presented with a 6-year history of recurrent hypoglycemia with multiple lesions in liver. Admission workup revealed elevated serum insulin and C-peptide, as well as multiple lesions in the liver (largest being 4.3 cm), enlarged lymph nodes around the pancreas, and a lesion (of 3.5 cm) at the proximal jejunum, as shown by contrast computed tomography (CT). Liver biopsy showed the lesions to be well-differentiated neuroendocrine tumors, grade G1...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29659121/glucagon-like-peptide-1-ameliorates-cardiac-lipotoxicity-in-diabetic-cardiomyopathy-via-the-ppar%C3%AE-pathway
#2
Lujin Wu, Ke Wang, Wei Wang, Zheng Wen, Peihua Wang, Lei Liu, Dao Wen Wang
Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4 and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high-fat diets were significantly reversed by exendin-4 and saxagliptin treatments for 8 weeks...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29650350/loss-of-dorsomedial-hypothalamic-glp-1-signaling-reduces-bat-thermogenesis-and-increases-adiposity
#3
Shin J Lee, Graciela Sanchez-Watts, Jean-Philippe Krieger, Angelica Pignalosa, Puck N Norell, Alyssa Cortella, Klaus G Pettersen, Dubravka Vrdoljak, Matthew R Hayes, Scott Kanoski, Wolfgang Langhans, Alan G Watts
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate energy balance by controlling sympathetic outflow and BAT function. METHODS: We investigate this possibility in adult male rats by using direct administration of GLP-1 (0...
March 21, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29648441/biocompatible-polymers-modified-with-d-octaarginine-as-an-absorption-enhancer-for-nasal-peptide-delivery
#4
Kohei Miyata, Masami Ukawa, Kohta Mohri, Kozue Fujii, Mako Yamada, Sohei Tanishita, Satoshi Higashitarumi, Seiya Ishizaki, Hironori Kumagai, Kyohei Ochiai, Ken-Ichiro Hiwatari, Kazufumi Tsubaki, Koichi Shigeno, Etsuo Tobita, Hideo Kobayashi, Shinji Sakuma
Peptide and protein drugs, which are categorized as biologics, exhibit poor membrane permeability. This pharmacokinetic disadvantage has largely restricted the development of non-invasive dosage forms of biologics that deliver into systemic circulation. We have been investigating the potential use of cell-penetrating peptide-linked polymers as a novel absorption enhancer to overcome this challenge. Since our previous study revealed that biocompatible poly(N-vinylacetamide-co-acrylic acid) modified with D-octaarginine, a typical cell-penetrating peptide, enhanced in vitro permeation of biomolecules such as plasmid DNA and bovine serum albumin through cell membranes, the present study evaluated if the polymers enhanced in vivo absorption of biologics applied on the mucosa...
April 12, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29626654/geniposide-improves-repeated-restraint-stress-induced-depression-like-behavior-in-mice-by-ameliorating-neuronal-apoptosis-via-regulating-glp-1r-akt-signaling-pathway
#5
Yinghua Zhao, Hongyan Li, Fang Fang, Tingting Qin, Wei Xiao, Zhenzhong Wang, Shiping Ma
Geniposide (GP), a bioactive iridoid glycoside isolated from Gardenia jasminoides Ellis, as well as an agonist of Glucagon-like peptide-1 receptor (GLP-1R), has been reported to exhibit antidepressant-like effects in several rodent models. However, the underlying mechanisms remain obscure. In this study, we mainly investigated the antidepressant-like effects of GP and explored the possible mechanisms associated with GLP-1R signaling by using the repeated restraint stress (RRS)-induced depression model of mice...
April 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29621668/exendin-4-relieves-the-inhibitory-effects-of-high-glucose-on-the-proliferation-and-osteoblastic-differentiation-of-periodontal-ligament-stem-cells
#6
Zijun Guo, Rui Chen, Fujun Zhang, Ming Ding, Ping Wang
BACKGROUND: With the impaired regenerative potential in patients with diabetes mellitus (DM), Periodontal ligament stem cells (PDLSCs) are regarded as an attractive source of stem cells for periodontal cytotherapy. Recent studies have shown that Exendin-4 (Ex-4) exerts cell-protective effects and bone remodeling ability on many types of cells. The aim of this study was to investigate whether Ex-4 alleviates the inhibition of high glucose on the proliferation and osteogenic differentiation of PDLSCs...
March 27, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29607314/glucagon-like-peptide-1-mediates-the-protective-effect-of-the-dipeptidyl-peptidase-iv-inhibitor-on-renal-fibrosis-via-reducing-the-phenotypic-conversion-of-renal-microvascular-cells-in-monocrotaline-treated-rats
#7
Jian Xu, Jingjing Wang, Yusheng Cheng, Xiang Li, Mengyu He, Jiali Zhu, Honghao Han, Guihong Wei, Hui Kong, Weiping Xie, Hong Wang, Xiangrong Zuo
Chronic kidney diseases are characterized by renal fibrosis with excessive matrix deposition, leading to a progressive loss of functional renal parenchyma and, eventually, renal failure. Renal microcirculation lesions, including the phenotypic conversion of vascular cells, contribute to renal fibrosis. Here, renal microcirculation lesions were established with monocrotaline (MCT, 60 mg/kg). Sitagliptin (40 mg/kg/d), a classical dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the renal microcirculation lesions by inhibiting glomerular tuft hypertrophy, glomerular mesangial expansion, and microvascular thrombosis...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29603687/mir-7-mir-9-and-mir-375-contribute-to-effect-of-exendin-4-on-pancreatic-%C3%AE-cells-in-high-fat-diet-fed-mice
#8
Chang Guo, Yi-Qiong Sun, Qiang Li, Jin-Chao Zhang
PURPOSE: The purpose of this study was to test whether glucagon-like peptide-1 (GLP-1) receptor activation preserved pancreatic β-cells via the regulation of microRNAs and target genes in high-fat-diet-fed mice. METHODS: C57BL/6 male mice were simultaneously treated with high-fat-diet (HFD) and GLP-1 analogue, Exendin-4 (Ex-4) (3 μg/kg/day or 30 μg/kg/day), i.p. or vehicle, for consecutive 13 weeks. Fasting blood glucose, postprandial blood glucose, ΔI30/ΔG30, HOMA-IR and HOMA-% β were measured in each group...
March 27, 2018: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/29597167/engineering-a-novel-protease-based-exendin-4-derivative-for-type-2-antidiabetic-therapeutics
#9
Xia Zhong, Shaomin Yang, Tianxiang Liu, Shundong Ji, Jinrui Hu, Hongjian Li
To develop an effective long-acting antidiabetic agent, we designed a novel Exendin-4 derivative (termed LEx4) containing an albumin-binding domain (ABD), a protease-cleavable linker and a native Exendin-4. Here, we present the LEx4 with balanced glucoregulatory activity and prolonged in vivo activity. As a first step, the LEx4 with purity more than 99% was prepared. Microscale thermophoresis (MST) results demonstrated that LEx4 associates with rat and monkey serum albumin with high-affinity (Ka  = 1.26 × 106  M-1 and 1...
March 21, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29593427/glucagon-like-peptide-1-exerts-anti-inflammatory-effects-on-mouse-colon-smooth-muscle-cells-through-the-cyclic-adenosine-monophosphate-nuclear-factor-%C3%AE%C2%BAb-pathway-in-vitro
#10
Ahmed Al-Dwairi, Tamara E Alqudah, Othman Al-Shboul, Mohammad Alqudah, Ayman G Mustafa, Mahmoud A Alfaqih
Background: Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. Aim: The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS)...
2018: Journal of Inflammation Research
https://www.readbyqxmd.com/read/29579298/long-lasting-glucagon-like-peptide-1-analogue-exendin-4-ameliorates-the-secretory-and-synthetic-function-of-islets-isolated-from-severely-scalded-rats
#11
Dongxu Zhao, Li Ma, Chuanan Shen, Dawei Li, Wenfeng Cheng, Yuru Shang, Zhaoxing Liu, Xin Wang, Kai Yin
The aim of this article was to observe the intracellular insulin content of islets isolated from severely scalded and Exendin-4-treated rats and to evaluate the stimulation of insulin mRNA synthesis and secretion by β cells at different glucose concentrations and during different periods of time. A 50% TBSA full-thickness scalded rat model was used. Rats were treated with Exendin-4, followed by islet isolation and functional measurements. Serum was collected for detection of serum insulin, glucose, and glucagon levels...
March 20, 2018: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/29533738/intragastric-nutrient-infusion-reduces-motivation-for-food-in-male-and-female-rats
#12
Calyn B Maske, Gregory C Loney, Nicole Lilly, Sarah J Terrill, Diana L Williams
The idea that gut-derived satiation signals influence food reward has recently gained traction, but this hypothesis is largely based on studies focused on neural circuitry, not the peripherally released signals. Here, we directly tested the hypothesis that intragastric (IG) nutrient infusion can suppress motivation for food. In a series of experiments, IG sucrose infusion (15 kcal) significantly and reliably reduced operant responding for a sucrose reward on a progressive ratio (PR) schedule. Moreover, food deprivation for 24 h before the test session did not prevent the suppressive effect of nutrients...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29530599/the-glucagon-like-peptide-1-glp-1-analog-liraglutide-attenuates-renal-fibrosis
#13
Ya-Kun Li, Dong-Xia Ma, Zhi-Min Wang, Xiao-Fan Hu, Shang-Lin Li, Hong-Zhe Tian, Meng-Jun Wang, Yan-Wen Shu, Jun Yang
Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29526117/metabonomic-analysis-of-the-therapeutic-effect-of-exendin-4-for-the-treatment-of-tbhp-induced-injury-in-mouse-glomerulus-mesangial-cells
#14
Linxi Wang, Zhiqing Liu, Zhou Chen, Caihua Huang, Xiaohong Liu, Can Chen, Xiaoyin Liu, Jingze Huang, Libin Liu, Donghai Lin
Although previous studies have reported the protective effect of glucagon-like peptide-1 (GLP-1) in diabetes nephropathy, the molecular mechanism such as nephroprotection remains elusive. In this study, we explored the molecular mechanism of exendin-4 as an GLP-1 receptor agonist for the treatment of tert-butyl hydroperoxide (t-BHP)-induced injury in mouse glomerulus mesangial cells (SV40 MES 13 cells) via an NMR-based metabonomic analysis. We found that exendin-4 protected mesangial cells from t-BHP-mediated toxicity, decreased the percentage of t-BHP-treated cells undergoing apoptosis, and restored glucose consumption in the t-BHP-treated group...
March 12, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29523188/azoramide-a-novel-regulator-favors-adipogenesis-against-osteogenesis-through-inhibiting-the-glp-1-receptor-pka-%C3%AE-catenin-pathway
#15
Banjun Ruan, Zheng Zhu, Zhao Yan, Wei Yang, Dongsheng Zhai, Li Wang, Zichen Ye, Huanyu Lu, An Xiang, Jingwei Liang, Yinghao Jiang, Chengming Xu, Zhenyu Wang, Ming Wei, Xiaoying Lei, Xiaorui Cao, Zifan Lu
BACKGROUND: The reciprocal fate decision of mesenchymal stem cells (MSCs) to either bone or adipocytes is determined by Wnt-related signaling and the glucagon-like peptide-1 receptor (GLP-1R). Azoramide, an ER stress alleviator, was reported to have an antidiabetic effect. In this study, we investigated the function of azoramide in regulating the lineage determination of MSCs for either adipogenic or osteogenic differentiation. METHODS: In this study, microcomputed tomography and histological analysis on bone morphogenetic protein (BMP)2-induced parietal periosteum bone formation assays, C3H10T1/2 and mouse bone marrow MSC-derived bone formation and adipogenesis assays, and specific staining for bone tissue and lipid droplets were used to evaluate the role of azoramide on the lineage determination of MSC differentiation...
March 9, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29522713/replacement-of-the-c-terminal-trp-cage-of-exendin-4-with-a-fatty-acid-improves-therapeutic-utility
#16
Jung Gi Lee, Jae Ha Ryu, Seon-Myung Kim, Moon-Young Park, San-Ho Kim, Young G Shin, Jong-Woo Sohn, Ha Hyung Kim, Zee-Yong Park, Jae Young Seong, Jae Il Kim
Exendin-4, a 39 amino acid peptide isolated from the saliva of the Gila monster, plays an important role in regulating glucose homeostasis, and is used clinically for the treatment of type 2 diabetes. Exendin-4 shares 53% sequence identity with the incretin hormone glucagon-like peptide 1 (GLP-1) but, unlike GLP-1, is highly resistant to proteolytic enzymes such as dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase 24.11 (NEP 24.11). Herein, we focused on the structure and function of the C-terminal Trp-cage of exendin-4, and suggest that it may be structurally required for resistance to proteolysis by NEP 24...
March 6, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29517636/a-new-2-step-acceleration-protocol-using-a-histone-deacetylase-inhibitor-to-generate-insulin-producing-cells-from-adipose-derived-mesenchymal-stem-cells
#17
Tetsuya Ikemoto, Rui Feng, Mitsuo Shimada, Yu Saito, Shuichi Iwahashi, Yuji Morine, Satoru Imura
OBJECTIVES: We aimed to develop a simple protocol for deriving insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ADSCs). We established a 2-step creation method and an acceleration strategy with a histone deacetylase inhibitor that promoted a pro-endocrine pancreatic lineage. METHODS: We seeded ADSCs in 96-well dishes and cultured in Dulbecco's modified Eagle's medium/F12 medium containing 1% fetal bovine serum, 1% B27 supplement, 1% N2 supplement, 50-ng/mL human activin A, and 10-nM exendin-4 for step 1 of differentiation (7 days)...
April 2018: Pancreas
https://www.readbyqxmd.com/read/29515208/exendin-4-modifies-adipogenesis-of-human-adipose-derived-stromal-cells-isolated-from-omentum-through-multiple-mechanisms
#18
Xiaoying He, Hongyu Guan, Weiwei Liang, Zhimin Huang, Lijuan Xu, Pengyuan Zhang, Fen Xu, Yanbing Li
BACKGROUND: Abdominal obesity is considered a major factor in the development of metabolic disorders. Glucagon-like peptide-1 (GLP-1) has been reported to have positive effects on improving body metabolism and to reducing insulin resistance. However, it remains less clear whether GLP-1 plays a role in the adipogenesis process of visceral fat. METHODS: Here, we analyzed the in vitro actions and probable mechanisms of Exendin-4, a GLP-1 receptor agonist, on human adipose-derived stromal cells (hADSCs) isolated from omentum...
February 8, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29510158/endogenous-glp-1-in-lateral-septum-contributes-to-stress-induced-hypophagia
#19
Sarah J Terrill, Calyn B Maske, Diana L Williams
Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the lateral septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with bilateral cannulas targeting the dorsal subregion of the LS (dLS)...
March 3, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29503858/radiosynthesis-and-evaluation-of-an-18-f-labeled-silicon-containing-exendin-4-peptide-as-a-pet-probe-for-imaging-insulinoma
#20
Lukas O Dialer, Andreas Jodal, Roger Schibli, Simon M Ametamey, Martin Béhé
Background: Analogues of exendin-4 have been radiolabeled for imaging the glucagon-like peptide type 1 receptors (GLP-1R) which are overexpressed in insulinoma. The aim of this research was to synthesize an18 F-labeled silicon containing exendin-4 peptide (18 F- 2 ) and to evaluate its in vitro and in vivo behavior in CHL-GLP-1 receptor positive tumor-bearing mice.18 F-labeled silicon containing exendin-4 peptide (18 F- 2 ) was prepared via one-step nucleophilic substitution of a silane precursor with18 F-fluoride in the presence of acetic acid and K222...
2018: EJNMMI Radiopharmacy and Chemistry
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