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Christina Pedersen, Trine Porsgaard, Maria Thomsen, Mette Marie Rosenkilde, Nikolaj Kulahin Roed
Insulin is a vital part of diabetes treatment, whereas glucagon is primarily used to treat insulin-induced hypoglycemia. However, glucagon is suggested to have a central role in the regulation of body weight, which would be beneficial for diabetic patients. Since the glucagon effect on blood glucose is known to be transient, it is relevant to investigate the pharmacodynamics of glucagon after repeated dosing. In the present study, we used telemetry to continuously measure blood glucose in streptozotocin induced diabetic Sprague-Dawley rats...
2018: PloS One
Carol H Wysham, Dominic Pilon, Mike Ingham, Marie-Hélène Lafeuille, Bruno Emond, Rhiannon Kamstra, Michael Pfeifer, Patrick Lefebvre
OBJECTIVE: To compare achievement of quality goals (HbA1c, weight loss/body mass index[BMI], systolic blood pressure[SBP]), including maintaining HbA1c, between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300mg (CANA) or a GLP-1 in an actual practice setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 were identified from the IQVIATM Real-World Data Electronic Medical Records - US database (2012Q2-2016Q1). To account for differences in baseline characteristics, inverse probability of treatment weighting was used...
March 20, 2018: Current Medical Research and Opinion
Dandan Zhao, Shaoqian Zhao, Xiao Wang, Mingbo Su, Wen Liu, Qinyun Ma, Jie Hong, Weiqiong Gu, Jingya Li, Ruixin Liu, Guang Ning, Jiqiu Wang, Yifei Zhang
The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects...
2018: Frontiers in Endocrinology
Xiping Cheng, Sun Y Kim, Haruka Okamoto, Yurong Xin, George D Yancopoulos, Andrew J Murphy, Jesper Gromada
Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/β-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/β-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/β-catenin...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Harumi Takahashi, Shihomi Hidaka, Chihiro Seki, Norihide Yokoi, Susumu Seino
The dynamics of insulin secretion stimulated by repaglinide, a glinide, and the combinatorial effects of repaglinide and incretin were investigated. At 4.4mM glucose, repaglinide induced insulin secretion with a gradually increasing first phase, showing different dynamics from that induced by glimepiride, a sulfonylurea. In the presence of glucagon-like peptide-1 (GLP-1), insulin secretion by repaglinide was augmented significantly but to lesser extent and showed different dynamics from that by glimepiride...
March 16, 2018: European Journal of Pharmacology
Hong-Quan Luo, Wei-Wang Gu, Li-Wen Huang, Li-Hong Wu, Yu-Guang Tian, Chun-Hua Zheng, Min Yue
Obesity is a public health problem in both developed and developing countries, and the negative effects of obesity on reproductive physiology have been highlighted recently. We evaluated the effects of porcine obesity index, sex hormones, and peptide hormones on litter size in various breeds of minipigs. Blood samples were collected from sedated 8-,10-, and 12-mo-old minipigs to measure preovulatory levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin) and peptide hormones (insulin-like growth factor, glucagon, cortisol, growth hormone, free thyroxine, free triiodothyronine, insulin, and leptin)...
March 1, 2018: Journal of the American Association for Laboratory Animal Science: JAALAS
Jacqueline H Parilla, Rebecca L Hull, Sakeneh Zraika
Neprilysin (NEP) is an endopeptidase known to modulate nervous, cardiovascular, and immune systems via inactivation of regulatory peptides. In addition, it may also contribute to impaired glucose homeostasis as observed in type 2 diabetes (T2D). Specifically, we and others have shown that NEP is upregulated under conditions associated with T2D, whereas NEP deficiency and/or inhibition improves glucose homeostasis via enhanced glucose tolerance, insulin sensitivity, and pancreatic β-cell function. Whether increased β-cell mass also occurs with lack of NEP activity is unknown...
March 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Keiichi Torimoto, Yosuke Okada, Yoshiya Tanaka
Vascular endothelial function is important for maintaining the homeostasis of the living body. Especially, nitric oxide (NO) produced in vascular endothelial cells regulates blood vessel tone and has an antiatherosclerotic effect. Type 2 diabetes is a typical disease that causes impaired vascular endothelial function, resulting in various vascular complications and damage to organs. Cardiovascular disease associated with type 2 diabetes is a chronic inflammatory disease that starts with endothelial dysfunction (ED), and vascular ED is important as an initial change in arteriosclerotic lesions...
2018: Journal of UOEH
Akira Kurozumi, Yosuke Okada, Kei Sugai, Keiichi Torimoto, Yoshiya Tanaka
Our purpose was to determine the effects of teneligliptin and sitagliptin, two dipeptidyl peptidase 4 inhibitors (DPP4-Is) with different half-lives, on glycemic variability and glucagon-like peptide-1 (GLP-1) levels in Japanese patients with type 2 diabetes mellitus (T2DM). The study subjects were 14 drug-naïve patients with T2DM who were allocated to either a 20 mg/day teneligliptin group (n = 7) or a 50 mg/day sitagliptin group (n = 7) for 7 days, then switched to the other treatment for another 7 days...
2018: Journal of UOEH
Caitlin Sandman, Benjamin Krainin, Jamie Roper
BACKGROUND: Type II diabetes mellitus (DM) is an increasingly prevalent cause of morbidity and mortality among U.S. adults, with increasing prevalence in emergency department (ED) visits. Multiple medications, such as exenatide, a glucagon-like peptide-1 agonist, have been developed in the past decade to combat this growing problem. This medication is well documented to cause gastrointestinal upset and skin nodules at the injection site. However, currently no documented cases exist regarding manipulation of injection nodules causing increased absorption or reports demonstrating an increase in adverse drug reactions...
March 15, 2018: Journal of Emergency Medicine
M Sassek, E Pruszynska-Oszmalek, K W Nowak
The physiology of porcine pancreatic islets is poorly understood. Orexin A is one of important agents regulating the physiology of porcine pancreatic islets. This study aimed to determine the potential effect of orexin A on the functioning of porcine pancreatic islets. Orexin receptor localization was done by PCR (polymerase chain reaction) and Western Blot, both in pancreatic isolated islets and whole pancreas. Secretion of insulin and glucagon from islets after orexin-A treatment was assayed. The viability of pig pancreatic islet cells and level of cleaved/total caspase 3 protein were measured by MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Western blotting, respectively...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
March 9, 2018: Epilepsy Research
Vishal Musale, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon, Maria Luisa Mangoni
Long-standing Type 2 diabetes is associated with loss of both β-cell function and β-cell mass. Peptides derived from the frog-skin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin-1a(1-21).NH2 , esculentin-1b(1-18).NH2 , and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1...
March 17, 2018: Amino Acids
Keisuke Fukumura, Takahiro Konuma, Yusuke Tsukamoto, Shinji Nagata
Adipokinetic hormone (AKH), an analog of mammalian glucagon, functions in supplying the required energy by releasing lipids and carbohydrates from the fat body into the hemolymph. Our previous study showed that AKH receptor (AKHR) knockdown in the two-spotted cricket Gryllus bimaculatus decreased hemolymph lipid levels and increased its feeding frequency. To reveal underlying mechanisms by which AKH signaling modulates lipid homeostasis, we analyzed the fatty acid composition as the lipid structure in the crickets...
March 16, 2018: Scientific Reports
Anita D Misra-Hebert, Kevin M Pantalone, Xinge Ji, Alex Milinovich, Tanujit Dey, Kevin M Chagin, Janine M Bauman, Michael W Kattan, Robert S Zimmerman
OBJECTIVE: To identify severe hypoglycemia events, defined as emergency department visits or hospitalizations for hypoglycemia, in patients with type 2 diabetes receiving care in a large health system and to identify patient characteristics associated with severe hypoglycemia events. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study from January 2006 to December 2015 using the electronic medical record in the Cleveland Clinic Health System (CCHS)...
March 16, 2018: Diabetes Care
Luisella Bocchio Chiavetto, Roberta Zanardini, Sarah Tosato, Mariacarla Ventriglia, Clarissa Ferrari, Chiara Bonetto, Antonio Lasalvia, Franco Giubilini, Angelo Fioritti, Francesca Pileggi, Michela Pratelli, Michele Pavanati, Angela Favaro, Giovanni De Girolamo, Giovanni Battista Frisoni, Mirella Ruggeri, Massimo Gennarelli
The molecular underpinnings associated to first episode psychosis (FEP) remains to be elucidated, but compelling evidence supported an association of FEP with blood alterations in biomarkers related to immune system, growth factors and metabolism regulators. Many of these studies have not been already confirmed in larger samples or have not considered the FEP diagnostic subgroups. In order to identify biochemical signatures of FEP, the serum levels of the growth factors BDNF and VEGF, the immune regulators IL-1RA, IL-6, IL-10 and IL-17, RANTES/CCL5, MIP-1b/CCL4, IL-8 and the metabolic regulators C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin and visfatin were analysed in 260 subjects collected in the GET UP project...
March 13, 2018: Brain, Behavior, and Immunity
Geoffrey P Roberts, Richard G Kay, James Howard, Richard H Hardwick, Frank Reimann, Fiona M Gribble
BACKGROUND: Altered enteroendocrine hormone responses are widely believed to underlie the beneficial effects of bariatric surgery in type 2 diabetes. While elevated postprandial glucagon-like peptide-1 (GLP-1) is considered one of the mediators, increased postprandial glucagon levels have recently been implicated. OBJECTIVES: We investigated hormonal responses in lean patients after prophylactic total gastrectomy (PTG), as a model of Roux-en-Y gastric bypass without the confounding effects of obesity or massive weight loss...
February 3, 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Line Engelbrechtsen, Yuvaraj Mahendran, Anna Jonsson, Anette Prior Gjesing, Peter E Weeke, Marit E Jørgensen, Kristine Færch, Daniel R Witte, Jens J Holst, Torben Jørgensen, Niels Grarup, Oluf Pedersen, Henrik Vestergaard, Signe Torekov, Jørgen K Kanters, Torben Hansen
BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis...
March 16, 2018: BMC Genetics
Darshan Khangura, L Romayne Kurukulasuriya, Adam Whaley-Connell, James R Sowers
The presence of hypertension in individuals with type 2 diabetes augments the risk for cardiovascular morbidity and mortality. In this regard, data support that management of hypertension in this high-risk population is a critical risk reduction strategy. In recent years, a number of work groups have redefined hypertension, management strategies, and targets. In this context, there is still considerable discussion on an appropriate target for blood pressure in the diabetic population. However, despite this discussion on target blood pressure, it is widely recognized that there is considerable residual risk for heightened cardiovascular events in the hypertensive, diabetic population despite widespread awareness and treatment...
March 14, 2018: American Journal of Hypertension
Rika Fukumori, Yoji Masuda, Ayaka Takeuchi, Rina Yanai, Khurchabiling Atchalalt, Borjigin Sarentonglaga, Kazuko Ogata, Mio Yamaguchi, Asuka Hara, Akane Sato, Toshihisa Sugino, Yoshikazu Nagao
The aim of this study was to investigate how intra-duodenal infusions of fatty acids (FA) affect appetite-related gut peptides such as glucagon-like peptide-1 (GLP-1) and ghrelin in sheep. We hypothesized that these peptides can be highly reactive to unsaturated long-chain FA, because they are well known to decrease DMI. Four ewes were fitted with a duodenal cannula and a jugular vein catheter for a 6-h duodenal infusion of the nine FA (C8:0, C10:0, C12:0, C14:0, C16:0, C18:0, C18:1, C18:2, C18:3) and water (control)...
March 14, 2018: Journal of Animal Science
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