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Gastrointestinal Hormones (gastrointestinal + hormones)
Selected AbstractsRole of Gastrointestinal Hormones in Postprandial Reduction of Bone Resorption,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2003Dennis B Henriksen Abstract Collagen type I fragments, reflecting bone resorption, and release of gut hormones were investigated after a meal. Investigations led to a dose escalation study with glucagon like peptide-2 (GLP-2) in postmenopausal women. We found a dose-dependent effect of GLP-2 on the reduction of bone resorption. Introduction: The C-terminal telopeptide region of type I collagen as measured in serum (s-CTX) can be used to assess bone resorption. This marker of bone resorption has a significant circadian variation that is influenced by food intake. However, the mediator of this variation has not been identified. Materials and Methods: We studied the release of the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2; a representative of the intestinal proglucagon-derived peptides) after ingestion of glucose, fat, protein, and fructose, as well as their effects after parenteral administration in relation to bone turnover processes in healthy volunteers. Furthermore, we studied the effect on bone turnover of a single subcutaneous injection of GLP-2 in four different dosages (100, 200, 400, or 800 ,g GLP-2) or placebo in 60 postmenopausal women (mean age, 61 ± 5 years). Results: All macronutrients significantly (p < 0.05) reduced bone resorption as assessed by s-CTX (39,52% from baseline), and only the glucagon-like peptides were secreted in parallel. Parenteral administration of GIP and GLP-1 did not result in a reduction of the s-CTX level, whereas GLP-2 caused a statistically significant and dose-dependent reduction in the s-CTX level from baseline compared with placebo (p < 0.05). Urine DPD/creatinine, a marker of bone resorption, was significantly reduced by 25% from baseline in the 800-,g GLP-2 group (p < 0.01). An area under the curve (AUC0,8h) analysis for s-CTX after GLP-2 injection confirmed the dose-dependent decrease (ANOVA, p = 0.05). The s-osteocalcin level was unaffected by the GLP-2 treatment. Conclusion: These studies exclude both GIP and GLP-1 as key mediators for the immediate reduction in bone resorption seen after a meal. The dose-dependent reduction of bone resorption markers found after subcutaneous injection of GLP-2 warrants further investigation into the mechanism and importance of GLP-2 for the bone turnover processes. [source] RD Lawrence Lecture 2008 Targeting GLP-1 release as a potential strategy for the therapy of Type 2 diabetesDIABETIC MEDICINE, Issue 8 2008F. M. Gribble Abstract Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal hormones that play an important role in stimulating postprandial insulin release from pancreatic ,-cells. Agents that either mimic GLP-1 or prevent its degradation are now available for the treatment of Type 2 diabetes, and strategies to enhance endogenous GLP-1 release are under assessment. As intestinal peptides have a range of actions, including appetite regulation and coordination of fat metabolism, harnessing the enteric endocrine system is a promising new field for drug development. [source] Microscale characterization of the binding specificity and affinity of a monoclonal antisulfotyrosyl IgG antibodyELECTROPHORESIS, Issue 12 2008Klaus S. Lassen Dr. Abstract Sulfation is a potentially important post-translational modification of proteins and has been demonstrated in a number of polypeptides, notably in gastrointestinal hormones. In contrast to phosphorylation, however, the investigation of sulfation patterns in tissues and on purified proteins has been complicated by the absence of specific immunoreagents (antibodies) for this modification as well as the chemical lability of the sulfate group. Here, we investigate the properties of a novel mAb against sulfated tyrosyl groups (anti-Tyr(SO3H) antibody) using CE and a panel of sulfated and nonsulfated peptides and proteins. The data show that the anti-Tyr(SO3H) antibody is completely specific for compounds containing sulfated tyrosyls. Affinity electrophoresis experiments allowed us to estimate dissociation constants for sulfated hirudin fragment (56,65), gastrin-17, and cholecystokinin octapeptide (CCK8) in the 1,3,,M range. The affinity of the antibody toward complement 4 protein that contains three sulfotyrosines was analyzed by surface plasmon resonance technology and modeled according to a bivalent-binding model which yielded a Kd1 of 20.1,,M for the monovalent complex. The same binding was studied by CE and found to be in the micromolar scale albeit with some uncertainty due to complex separation patterns. The work illustrates the amount of information on antibody,antigen interactions that may be obtained with microelectrophoretic methods consuming minute quantities of material. Furthermore the specificity of this antibody could be confirmed in one operation using an array of sulfated and nonsulfated compounds. [source] Gut,Brain Axis: Regulation of Glucose MetabolismJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2006A. C. Heijboer Obesity and type II diabetes mellitus have reached epidemic proportions. From this perspective, knowledge about the regulation of satiety and food intake is more important than ever. The gut releases several peptides upon feeding, which affect hypothalamic pathways involved in the regulation of satiety and metabolism. Within the hypothalamus, there are complex interactions between many nuclei of which the arcuate nucleus is considered as one of the most important hypothalamic centres that regulates food intake. The neuropeptides, which are present in the hypothalamus and are involved in regulating food intake, also play a key role in regulating glucose metabolism and energy expenditure. In synchrony with the effects of those neuropeptides, gastrointestinal hormones also affect glucose metabolism and energy expenditure. In this review, the effects of the gastrointestinal hormones ghrelin, cholecystokinin, peptide YY, glucagon-like peptide, oxyntomodulin and gastric inhibitory polypeptide on glucose and energy metabolism are reviewed. These gut hormones affect glucose metabolism at different levels: by altering food intake and body weight, and thereby insulin sensitivity; by affecting gastric delay and gut motility, and thereby meal-related fluctuations in glucose levels; by affecting insulin secretion, and thereby plasma glucose levels, and by affecting tissue specific insulin sensitivity of glucose metabolism. These observations point to the notion of a major role of the gut,brain axis in the integrative physiology of whole body fuel metabolism. [source] Regulation of cholangiocyte proliferationLIVER INTERNATIONAL, Issue 2 2001Gene LeSage Abstract: Intrahepatic bile duct epithelial cells (i.e., cholangiocytes) are the target cells of chronic cholestatic liver diseases (i.e., cholangiopathies), which makes these cells of great interest to clinical hepatologists. This review will focus on "typical" cholangiocyte proliferation, whereas "atypical" (extension of cholangiocyte proliferation into parenchyma), and premalignant "oval" cell proliferation are reviewed elsewhere. The bile duct ligated (BDL) rat model, where most of the known mechanisms of cholangiocyte proliferation have been illustrated, was the first and remains the prototype animal model for "typical" cholangiocyte proliferation. Following a short overview of cholangiocyte functions, we briefly discuss the: (i) in vivo models [i.e., BDL (Fig. 1 and 4), chronic ,-naphthylisothiocyanate (ANIT) or bile acid feeding (Fig. 2), acute carbon tetrachloride (CCl4) feeding and partial hepatectomy; and (ii) in vitro experimental tools [e.g., purified cholangiocytes and isolated intrahepatic bile duct units (IBDU)] that are key to the understanding of the mechanisms of "typical" cholangiocyte growth. In the second part of the review, we discuss a number of potential factors or conditions [e.g., gastrointestinal hormones, nerves, estrogens, blood supply, and growth factors] as well as the intracellular mechanisms [e.g., adenosine 3,,5,-monophosphate (cAMP), and protein kinase C (PKC)] that may regulate "typical" cholangiocyte hyperplasia. Figure 1. Measurement of the number of intrahepatic bile ducts by histochemistry for ,-GT[a specific cholangiocyte marker (1, 3, 27)] in liver sections from normal rats [left] and rats that (immediately following bile duct ligation (BDL)) were infused by osmotic minipumps with 0.2% bovine serum albumin (BSA, control) [middle] or gastrin (2.5 nmol/kg/h) in 0.2% BSA [right] for 1 week. Following BDL [middle], there was a marked increase in the number of ducts as compared to normal rats [left]. Chronic gastrin infusion [right] markedly decreased the number of intrahepatic bile ducts as compared to BSA-treated BDL rats [middle]. Orig. magn., ×125. Reproduced with permission from reference (17). Figure 4. In situ immunohistochemistry for CK-19 [a cholangiocyte-specific marker (3)] in frozen liver sections n=6) from BDL [a] and BDL+vagotomy [b] rats. Note that vagotomy induced a marked decrease in the number of ducts as compared with BDL control rats. Orig. magn., ×125. Reproduced with permission from reference (11). Figure 2. In situ immunohistochemistry for cellular nuclear antigen (PCNA) in liver sections from normal rats [left] and normal rats fed 1% TC [middle] or 1% TLC [right] for 1 week. Chronic feeding of TC [middle] and TLC [right] induced a significant increase in the number of PCNA-positive cholangiocytes as compared with liver sections from normal rats [left]. Reproduced with permission from reference (7). [source] | ||||||||||