The Experts below are selected from a list of 44220 Experts worldwide ranked by ideXlab platform

Jens J Holst - One of the best experts on this subject based on the ideXlab platform.

Patricia L Brubaker - One of the best experts on this subject based on the ideXlab platform.

  • Current and potential therapeutic targets of Glucagon-Like Peptide-2.
    Current opinion in pharmacology, 2016
    Co-Authors: Kaori Austin, Melanie A. Markovic, Patricia L Brubaker
    Abstract:

    Glucagon-Like Peptide-2 (GLP-2) is a gut hormone that promotes highly specific growth and function of the intestinal epithelium. Recent studies have begun to elucidate the complex mechanism of action of GLP-2, which is mediated indirectly through other intestinal factors. Although a long-acting GLP-2 analog has recently been approved for treatment of adult patients with short bowel syndrome, there remain numerous conditions characterized by intestinal insufficiency for which pre-clinical studies, as well as some limited clinical data, support further consideration of GLP-2 for expanded therapeutic use.

  • Glucagon-Like Peptide-1: The missing link in the metabolic clock?
    Journal of diabetes investigation, 2016
    Co-Authors: Patricia L Brubaker, Manuel Gil-lozano
    Abstract:

    Circadian expression of clock genes in peripheral tissues is critical to the coordinated regulation of intestinal digestive and absorptive functions, insulin secretion, and peripheral tissue nutrient deposition during periods of nutrient ingestion, thereby preventing metabolic dysregulation. As Glucagon-Like Peptide-1 is a key incretin hormone that regulates glucose-dependent insulin secretion, we hypothesized that this intestinal hormone is a player in the peripheral metabolic clock, linking nutrient ingestion to insulin secretion. We have now established that secretion of Glucagon-Like Peptide-1 from the intestinal L cell shows a rhythmic pattern in rats and humans in vivo that is altered by circadian disruptors, such as constant light exposure, consumption of a Western diet and feeding at inappropriate times (i.e., during the light period in rodents). Interestingly, the alterations in the rhythm of the Glucagon-Like Peptide-1 secretory responses were found to parallel the changes in the pattern of insulin responses in association with significant impairments in glucose tolerance. Furthermore, we have detected circadian clock gene expression, and showed circadian secretion of Glucagon-Like Peptide-1 from both the murine and human L cell in vitro. These findings demonstrate that Glucagon-Like Peptide-1 is a functional component of the peripheral metabolic clock, and suggest that altered release of Glucagon-Like Peptide-1 might play a role in the metabolic perturbations that result from circadian disruption.

  • Glucagon-Like Peptide-2 increases dysplasia in rodent models of colon cancer.
    American Journal of Physiology-Gastrointestinal and Liver Physiology, 2012
    Co-Authors: Shivangi Trivedi, Stuart C. Wiber, Hala M.t. El-zimaity, Patricia L Brubaker
    Abstract:

    The intestinal hormone, Glucagon-Like Peptide-2 (GLP-2), enhances intestinal growth and reduces inflammation in rodent models. Hence, a degradation-resistant GLP-2 analog is under investigation for...

  • Glucagon-Like Peptide-1 TREATMENT DELAYS THE ONSET OF DIABETES IN 8 WEEK-OLD DB/DB MICE
    Diabetologia, 2002
    Co-Authors: Qinghua Wang, Patricia L Brubaker
    Abstract:

    Aims/hypothesis. Glucagon-Like Peptide-1 ameliorates the symptoms of diabetes through stimulation of insulin secretion and enhancement of beta-cell mass. We have therefore investigated the effects of Glucagon-Like Peptide-1 on the development of diabetes, using db/db mice as a model of Type II diabetes.

  • Oral delivery of Glucagon-Like Peptide-1 in a modified polymer preparation normalizes basal glycaemia in diabetic db/db mice.
    Diabetologia, 2000
    Co-Authors: J. W. Joseph, J. Kalitsky, S. St-pierre, Patricia L Brubaker
    Abstract:

    The insulinotropic hormone, Glucagon-Like Peptide-1 has been proposed for the treatment of patients with Type II (non-insulin-dependent) diabetes mellitus. As Glucagon-Like Peptide-1 is rapidly cleaved at L-ala2 by dipeptidylpeptidase IV, D-ala2-Glucagon-Like Peptide-1 was synthesized and shown to have dipeptidylpeptidase IV resistance in vitro and enhanced bioactivity in mice during an oral glucose challenge. The actions of D-ala2-Glucagon-Like Peptide-1 were, however, lost within 4 h of injection, thus necessitating frequent and invasive treatment if it is to be used therapeutically. To circumvent this problem, a microsphere of D-ala2-Glucagon-Like Peptide-1 that could be given orally was developed. We encapsulated D-ala2-Glucagon-Like Peptide-1 in poly(lactide-co-glycolide)-COOH with olive oil as a filler, using phase inversion. The microspheres were tested in vivo by oral gavage in mice at t = 0 h followed by repeated oral glucose tolerance tests at t = 0, 4 and 8 h. The D-ala2-Glucagon-Like Peptide-1-microspheres lowered the glycaemic response to the 4 h oral glucose challenge in both normal CD1 and diabetic db/db mice, by 41 +/- 12% (p <0.001) and 27 +/- 5% (p < 0.001), respectively and by 19 +/- 11% (p < 0.05) and 28 +/- 4% (p < 0.001), respectively during the 8-h test. At 4 h after the oral gavage, basal glycaemia in the diabetic mice was reduced from 13 +/- 1 mmol/l to 10 +/- 1 mmol/l and was reduced further 8h after treatment from 12 +/- 1 mmol/l to 8 +/- 1 mmol/l (p < 0.05). Giving D-ala2-Glucagon-Like Peptide-1 alone orally had no effect on glycaemia. The data presented here suggest that a similar microsphere preparation could be useful in the delivery of Glucagon-Like Peptide-1 to patients with Type II diabetes.

Daniel J Drucker - One of the best experts on this subject based on the ideXlab platform.

  • Glucagon-Like Peptide-2.
    Annual review of nutrition, 2006
    Co-Authors: Jennifer L. Estall, Daniel J Drucker
    Abstract:

    Multiple Peptide hormones produced within the gastrointestinal system aid in the regulation of energy homeostasis and metabolism. Among these is the intestinotrophic Peptide Glucagon-Like Peptide-2 (GLP-2), which is released following food intake and plays a significant role in the adaptive regulation of bowel mass and mucosal integrity. The discovery of GLP-2's potent growth-promoting and cytoprotective effects in the gastrointestinal (GI) tract stimulated interest in its use as a therapeutic agent for the treatment of GI diseases involving malabsorption, inflammation, and/or mucosal damage. Current research has focused on determining the physiological mechanisms contributing to the effects of GLP-2 and factors regulating its biological mechanisms of action. This chapter provides an overview of the biology of GLP-2 with a focus on the most recent findings on the role of this Peptide hormone in the normal and diseased GI tract.

  • Glucagon-Like Peptide 2 (GLP-2)
    Encyclopedia of Endocrine Diseases, 2004
    Co-Authors: Julie A. Lovshin, Daniel J Drucker
    Abstract:

    Glucagon-Like Peptide-2 (GLP-2), a 33-amino-acid proGlucagon-derived Peptide (PGDP), was first identified as a Peptide with intestinal growth factor-Like activity following experiments demonstrating that subcutaneously implanted Glucagon-producing tumors produced intestinal growth in nude mice. These observations were consistent with several case reports of intestinal mucosal hyperplasia in patients with Glucagon-producing tumors and experimental evidence linking increased PGDP expression with adaptation to intestinal injury in rodents and human subjects. Following intestinal injury or resection, the circulating levels of the PGDPs including GLP-2 rapidly increase in parallel with the adaptive response and growth of the remnant bowel.

  • Glucagon-Like Peptide-1 and Glucagon-Like Peptide-2
    Best practice & research. Clinical endocrinology & metabolism, 2004
    Co-Authors: Laurie L. Baggio, Daniel J Drucker
    Abstract:

    The Glucagon-Like Peptides (Glucagon-Like Peptide-1 (GLP-1) and Glucagon-Like Peptide-2 (GLP-2)) are released from enteroendocrine cells in response to nutrient ingestion. GLP-1 enhances glucose-stimulated insulin secretion and inhibits Glucagon secretion, gastric emptying and feeding. GLP-1 also has proliferative, neogenic and antiapoptotic effects on pancreatic β-cells. More recent studies illustrate a potential protective role for GLP-1 in the cardiovascular and central nervous systems. GLP-2 is an intestinal trophic Peptide that stimulates cell proliferation and inhibits apoptosis in the intestinal crypt compartment. GLP-2 also regulates intestinal glucose transport, food intake and gastric acid secretion and emptying, and improves intestinal barrier function. Thus, GLP-1 and GLP-2 exhibit a diverse array of metabolic, proliferative and cytoprotective actions with important clinical implications for the treatment of diabetes and gastrointestinal disease, respectively. This review will highlight our current understanding of the biology of GLP-1 and GLP-2, with an emphasis on both well-characterized and more novel therapeutic applications of these Peptides.

  • Glucagon-Like Peptide 2.
    The Journal of clinical endocrinology and metabolism, 2001
    Co-Authors: Daniel J Drucker
    Abstract:

    Glucagon-Like Peptide 2 (GLP-2) is a 33 amino acid Peptide-encoded carboxyterminal to the sequence of GLP-1 in the proGlucagon gene. Both GLP-1 and GLP-2 are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms of action. GLP-2 regulates gastric motility, gastric acid secretion, intestinal hexose transport, and increases the barrier function of the gut epithelium. GLP-2 significantly enhances the surface area of the mucosal epithelium via stimulation of crypt cell proliferation and inhibition of apoptosis in the enterocyte and crypt compartments. The cytoprotective and reparative effects of GLP-2 are evident in rodent models of experimental intestinal injury. GLP-2 reduces mortality and decreases mucosal injury, cytokine expression, and bacterial septicemia in the setting of small and large bowel inflammation. GLP-2 also enhances nutrient absorption and gut adaptation in rodents or humans with short bowel syndrome. The actions of GLP-2 are transduced by the GLP-2 receptor, a G protein-coupled receptor expressed in gut endocrine cells of the stomach, small bowel, and colon. Activation of GLP-2 receptor signaling in heterologous cells promotes resistance to apoptotic injury in vitro. The cytoprotective, reparative, and energy-retentive properties of GLP-2 suggests that GLP-2 may potentially be useful for the treatment of human disorders characterized by injury and/or dysfunction of the intestinal mucosal epithelium.

  • Circulating levels of Glucagon-Like Peptide-2 in human subjects with inflammatory bowel disease.
    American journal of physiology. Regulatory integrative and comparative physiology, 2000
    Co-Authors: Qiang Xiao, Daniel J Drucker, Robin P. Boushey, Maria Cino, Patricia L Brubaker
    Abstract:

    Glucagon-Like Peptide-2 (GLP-2) is a recently characterized intestine-derived Peptide that exerts trophic activity in the small and large intestine. Whether circulating levels of GLP-2 are perturbe...

Tianpei Hong - One of the best experts on this subject based on the ideXlab platform.

  • no pancreatic safety concern following Glucagon Like Peptide 1 receptor agonist therapies a pooled analysis of cardiovascular outcome trials
    Diabetes-metabolism Research and Reviews, 2018
    Co-Authors: Ye Liu, Qing Tian, Jin Yang, Haining Wang, Tianpei Hong
    Abstract:

    AIMS Evidence on the pancreatic safety of Glucagon-Like Peptide-1 receptor agonist therapy has been limited. The objective of the study was to investigate this issue by pooling data on the incidence of acute pancreatitis and pancreatic cancer from four large-scale cardiovascular outcome trials of Glucagon-Like Peptide-1 receptor agonists. MATERIALS AND METHODS Data were extracted from four published cardiovascular outcome trials of Glucagon-Like Peptide-1 receptor agonists in patients with type 2 diabetes, and pooled analysis was performed to evaluate the risk of acute pancreatitis and pancreatic cancer associated with Glucagon-Like Peptide-1 receptor agonist treatment. Peto OR with 95% CI was used for risk evaluation. RESULTS The four cardiovascular outcome trials enrolled a total of 33 457 patients with type 2 diabetes and reported 123 patients with acute pancreatitis and 70 patients with pancreatic cancer during the median follow-ups of 2.1 to 3.8 years. There was no increased risk of either acute pancreatitis (Peto OR 0.89 [95% CI 0.63, 1.27]) or pancreatic cancer (Peto OR 0.84 [95% CI 0.53, 1.35]) associated with Glucagon-Like Peptide-1 receptor agonists compared with placebo when added to standard care. CONCLUSIONS Combined analysis of the four cardiovascular outcome trials showed that treatment with Glucagon-Like Peptide-1 receptor agonists was not associated with an increased risk of either acute pancreatitis or pancreatic cancer in patients with type 2 diabetes. Our new analysis further supports the previously reported results.

  • No pancreatic safety concern following Glucagon‐Like Peptide‐1 receptor agonist therapies: A pooled analysis of cardiovascular outcome trials
    Diabetes metabolism research and reviews, 2018
    Co-Authors: Ye Liu, Qing Tian, Jin Yang, Haining Wang, Tianpei Hong
    Abstract:

    AIMS Evidence on the pancreatic safety of Glucagon-Like Peptide-1 receptor agonist therapy has been limited. The objective of the study was to investigate this issue by pooling data on the incidence of acute pancreatitis and pancreatic cancer from four large-scale cardiovascular outcome trials of Glucagon-Like Peptide-1 receptor agonists. MATERIALS AND METHODS Data were extracted from four published cardiovascular outcome trials of Glucagon-Like Peptide-1 receptor agonists in patients with type 2 diabetes, and pooled analysis was performed to evaluate the risk of acute pancreatitis and pancreatic cancer associated with Glucagon-Like Peptide-1 receptor agonist treatment. Peto OR with 95% CI was used for risk evaluation. RESULTS The four cardiovascular outcome trials enrolled a total of 33 457 patients with type 2 diabetes and reported 123 patients with acute pancreatitis and 70 patients with pancreatic cancer during the median follow-ups of 2.1 to 3.8 years. There was no increased risk of either acute pancreatitis (Peto OR 0.89 [95% CI 0.63, 1.27]) or pancreatic cancer (Peto OR 0.84 [95% CI 0.53, 1.35]) associated with Glucagon-Like Peptide-1 receptor agonists compared with placebo when added to standard care. CONCLUSIONS Combined analysis of the four cardiovascular outcome trials showed that treatment with Glucagon-Like Peptide-1 receptor agonists was not associated with an increased risk of either acute pancreatitis or pancreatic cancer in patients with type 2 diabetes. Our new analysis further supports the previously reported results.

Cathrine Orskov - One of the best experts on this subject based on the ideXlab platform.

  • the alpha cell expresses Glucagon Like Peptide 2 receptors and Glucagon Like Peptide 2 stimulates Glucagon secretion from the rat pancreas
    Diabetologia, 2007
    Co-Authors: J De Heer, Jens Pedersen, Cathrine Orskov, Jens J Holst
    Abstract:

    Aims/hypothesis Glucagon-Like Peptide-2 (GLP-2) is a gut hormone regulating intestinal growth and nutrient absorption. Recently, GLP-2 has been reported to stimulate Glucagon secretion in healthy humans. We sought to clarify the mechanism and physiological significance of this endocrine effect.

  • Structure, measurement, and secretion of human Glucagon-Like Peptide-2.
    Peptides, 2000
    Co-Authors: Bolette Hartmann, Cathrine Orskov, Anders H. Johnsen, Kim Adelhorst, Lars Thim, Jens J Holst
    Abstract:

    By using radioimmunoassays toward the cDNA-predicted amino acid sequence of human Glucagon-Like Peptide-2, a Peptide was isolated from extracts of human ileum. By mass spectrometry and Edman sequencing, this Peptide was identified as human proGlucagon 126-158. High-performance liquid chromatography analyses indicated that a similar immunoreactive Peptide (iGLP-2) was present in human plasma. Human plasma concentrations of iGLP-2 were elevated 3- to 4-fold at 1 to 2 h after ingestion of 800 to 1200 kcal meals.

  • Glucagon Like Peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans
    American Journal of Physiology-endocrinology and Metabolism, 1997
    Co-Authors: Michael A. Nauck, Cathrine Orskov, Jens J Holst, Ulrich Niedereichholz, Rainer Ettler, Robert Ritzel, Wolff Schmiegel
    Abstract:

    Glucagon-Like Peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological an...

  • Distribution of Glucagon-Like Peptide-1 and other preproGlucagon-derived Peptides in the rat hypothalamus and brainstem
    Neuroscience, 1997
    Co-Authors: Philip J. Larsen, Mads Tang-christensen, Jens J Holst, Cathrine Orskov
    Abstract:

    Central administration of the preproGlucagon-derived Peptide Glucagon-Like Peptide-1 significantly inhibits ingestion of food and water, and Glucagon-Like Peptide-1 binding sites are present in a multitude of central areas involved in the regulation of ingestional behaviour. To evaluate further the neuroanatomical organization of central Glucagon-Like Peptide-1 containing neuronal circuits with potential implications on ingestional behaviour, we carried out a series of experiments in the rat demonstrating the topographical sites of synthesis and processing of the preproGlucagon precursor followed by a chromatographic analysis of the processed fragments. In situ hybridization histochemistry revealed that preproGlucagon encoding messenger RNA was expressed in a single population of neurons in the caudal portion of the nucleus of the solitary tract. Gel chromatographic analysis of hypothalamic and brainstem tissue extracts revealed that the preproGlucagon precursor is processed in a fashion similar to that seen in the small intestine, preferentially giving rise to glicentin, Glucagon-Like Peptide-1 and Glucagon-Like Peptide-2. This single brain site of Glucagon-Like Peptide-1 synthesis was subsequently confirmed by immunohistochemical demonstration of Glucagon-Like Peptide-1-immunoreactive perikarya in the central and caudal parts of the nucleus of the solitary tract. Numerous sites containing Glucagon-Like Peptide-1 immunoreactive fibres were, however, discovered in the forebrain including hypothalamic, thalamic and cortical areas. The densest innervation by Glucagon-Like Peptide-1 immunoreactive nerve fibres was seen in the hypothalamic dorsomedial and paraventricular nuclei, but numerous Glucagon-Like Peptide-1 immunoreactive fibres were also seen throughout the periventricular strata of the third ventricle. Dual-labelling immunohistochemistry for tyrosine hydroxylase and Glucagon-Like Peptide-1 gave no evidence for co-localization of catecholamines and Glucagon-Like Peptide-1 in neurons of the lower brainstem. To identify neurons of the nucleus of the solitary tract that project to the hypothalamic paraventricular nucleus, the retrograde tracer FluoroGold was injected into this hypothalamic target and dual immunocytochemical identification of Glucagon-Like Peptide-1 and tyrosine hydroxylase-positive neurons was performed on brainstem sections containing retrogradely labelled perikarya. From this experiment it was seen that many of the retrogradely labelled neurons in the central portion of the nucleus of the solitary tract are catecholaminergic, while none is Glucagon-Like Peptide-1 immunoreactive. In contrast, most of the retrogradely labelled neurons of the caudal portion of the nucleus of the solitary tract contain Glucagon-Like Peptide-1. These observations further substantiate that Glucagon-Like Peptide-1 neurons of the solitary tract constitute a distinct non-catecholaminergic cell group which projects to many targets, one of which is the hypothalamic paraventricular nucleus.

  • Secretion of Glucagon-Like Peptide-1 and reactive hypoglycemia after partial gastrectomy
    Digestion, 1994
    Co-Authors: Jan Jesper Andreasen, Cathrine Orskov, Jens J Holst
    Abstract:

    Glucagon-Like Peptide-1 is a Peptide hormone from the distal small intestine which stimulates insulin secretion and inhibits Glucagon secretion and thereby lowers blood glucose. This hormone, therefor