Recently, knowledge about the physiological and physiopathological role of some already known gastrointestinal hormones has been increased. At the same time, new biologically active substances (peptides) have been isolated from the gastrointestinal tract and pancreas. Some hormones that were thought to be restricted to the digestive system have been identified in the brain and some peptides localized in the nervous terminals in the myenteric plexuses, actively participate in the biological process of the gut. These findings have made the comprehension of this field more complicated. As a consequence of this, the term of "gastrointestinal endocrinology" is emerging. In this article we will discuss some general concepts of gastrointestinal and pancreatic hormonal physio-pathology and individually, about the role of some hormones and peptides in the normal and abnormal biological process. We emphasize the importance of biochemical diagnosis of those abnormalities.
Publisher Summary The vasoactive intestinal peptide (VIP) was so named because of its isolation from the intestinal extracts and the potent vasodilator activity that guided its purification. The highest concentrations of VIP in the central nervous system are found in the cerebral cortex, suprachiasmatic nucleus, anterior olfactory nuclei, bed nucleus of stria terminalis, medial preoptic nucleus, nucleus accumbens, amygdala, striatum, hippocampus, central gray of the midbrain, and sacral spinal cord. VIP is a 28-amino-acid residue peptide that is structurally related to at least nine other peptides; together, they may be considered to belong to one of the several identifiable families of peptides. VIP-related peptides include peptide histidine isoleucine (PHI), peptide histidine methionine (PHM), secretin, glucagon, corticotropin-releasing factor (CRF), growth hormone-releasing factor (GRF), sauvagine, urotensin I, helodermin, and gastric inhibitory peptide (GIP). The structural features in common among these peptides account for some similarities that they exhibit in certain biological actions and some overlap in the binding to certain receptor sites. The structure of VIP is relatively well conserved through the animal kingdom. VIP has biological activity on a wide variety of organ systems and body functions, including central and peripheral neurons, and digestive, cardiovascular, respiratory, reproductive, exocrine, endocrine, neuroendocrine, immunologie, and renal functions. VIP is an important mediator or modulator of several basic physiological events, including the relaxation of vascular and nonvascular smooth muscle and the stimulation of water, electrolyte, macromolecular, and certain endocrine and neuroendocrine secretions.
Publisher Summary The pattern of gut hormone change in gastrointestinal disease falls to a considerable degree into a set pattern. Thus, malabsorption leads to an increase of the distal gut hormones, including neurotensin, enteroglucagon, and peptide tyrosine tyrosine (PYY). Neurotensin and PYY act to diminish acid secretion and delay intestinal transit, while enteroglucagon is associated in experimental animal models with the increased growth of the gut mucosa. Therefore, these influences are likely to act, at least in part, to enhance the absorption of nutriments. Motilin, on the other hand, tends to be elevated in diarrheal conditions and gastrin with hypochlorhydria. Glucose-dependent insulinotropic peptide (GIP) is diminished by disease or bypass of the upper small intestine, conditions that also delay the absorption of carbohydrates and that are associated with a delayed and diminished insulin response. These changes would fit with the possible role of GIP as the mediator of the enteroinsular axis. Secretin and cholecystokinin are diminished in the upper small intestinal mucosal disease, however, there is no evidence that cholecystokinin is increased in pancreatitis. Pancreatic polypeptide (PP) release is diminished in severe destructive disease of the pancreas but is variably elevated in other conditions. Measurement of the gut hormone profile in disease may provide clinically useful information as to the state of the gut.
Publisher Summary This chapter describes two apparently unrelated physiological phenomena for a single peptide that is gastric inhibitory polypeptide (GIP). These physiological actions are the inhibition of gastric acid secretion and stimulation of insulin release. GIP is a major hormone involved in the gastrointestinal regulation of insulin release, when glucose is ingested. This chapter provides an overview of these physiological actions of GIP. GIP has been shown to be a powerful inhibitor of gastric acid secretion from the Heidenhain-type pouch of the stomach of dog. The chapter also discusses the isolation, structure, and cellular localization of this peptide. The probable involvement of GIP in metabolic disturbances, such as obesity and diabetes, has been suggested. Recent studies using animal models have added significantly to the body of evidence supporting an involvement for GIP in metabolic disorders. The chapter further discusses the secretion of immunoreactive-GIP (IR–GIP). GIP has been shown to be insulinotropic in man, dog and rat, when administered intravenously at doses known to elevate serum levels to within the physiological range.
1. The insulinogenic factor of the gastrointestinal mucosa named "incretin" is only one part of the complex enteroinsular axis. --2. Of the chemically defined gastrointestinal hormones GIP is the strongest incretin candidate. --3. Because of the dual function of GIP as gastrone and insulinotropic substance several safeguards against GIP-mediated insulin hypoglycaemia exist. --4. No pathological condition has yet been found which is causally related to hyper- or hyposecretion of GIP. However, an exaggerated GIP response (usually secondary to the disease) may participate in the pathogenesis of hyperinsulinaemia of patients with obesity and duodenal ulcer. --5. The injection of GIP antibodies only partially abolishes the incretin effect. Therefore, GIP, although important, is not the only incretin.
Dr. Raymond Pederson, Dr. Jill Dryburgh and I commenced work on GIP in 1968, when, with the generous help of Professor Viktor Mutt and Professor Erik Jorpes of the Karolinska Inst,itute, Stockholm, we
Publisher Summary Within the gut, various gastrointestinal hormones are present in the cells of mucosal epithelium that tend to have defined, limited distributions in the various regions. This is in direct contrast to the peptide-containing nerves, which can be found at each level of the gut and which show few differential distributions. A range of different cytochemical methods have been applied in the identification and characterization of these cells and nerves, and in recent years, immunocytochemistry has emerged as a particularly useful technique in this field. With the advent of new technology, immunocytochemistry has become a reliable analytical tool. The biochemical study of peptide structures and their variant or precursor forms and the synthesis of appropriate fragments of peptide molecules, at present enables immunocytochemistry to identify cells that contain little active peptide. Information can be derived beyond just the localization of active peptides to their cells of origin. At present, it is possible to obtain data on cell or tissue function and on synthetic processing of peptides. These scientific developments and the improved availability of immunocytochemical methods and reagents have opened a new era in the cytochemical study of gut hormones.
Publisher Summary This chapter reviews some evolutionary aspects of gastrointestinal hormones. Modern interest in the phylogenetic aspects of the gut endocrine system is based on several more or less independent lines of study. Groups of gut hormones are related to each other by the similarities in amino acid sequence that is thought to indicate evolution by way of gene duplication and divergence. Families of gut hormones frequently include peptides that are found outside the gut endocrine system. The receptor sites at which gut hormones act are at present being characterized in greater detail and they can be shown to differ in their properties among species and among tissues. The chapter discusses the evolutionary significance of the recent work on mammalian gut peptides, together with the relevant comparative data. Many biologically active peptides first identified as gastrointestinal hormones are also present in brain where they are thought to have neurotransmitter-like functions; the reverse is also true. Peptides found in the brain have later been identified in gut endocrine cells. There is no support for the idea that the central nervous system (CNS) functions of the brain–gut peptides are exclusively concerned with digestion.
Publisher Summary Peptides with opioid activity, also termed endorphins, have a common amino terminus, Tyr-Gly-Gly-Phe-X, where X is either leucine (Leu) or methionine (Met). This free amino terminus is essential for opioid activity and the pentapeptide sequence is the minimum for significant opioid activity. This chapter discusses the opioid peptide systems and structures of the major opioid peptides. It reviews immunohistochemical distribution of opioid peptides. Opioid peptides have been observed in endocrine cells in the gastrointestinal tract of several species. The chapter also discusses the functional aspects of opioid peptides. The intrinsic power of opioid receptor-mediated effects suggests that opioid peptides are important in regulating gastrointestinal motility. Apart from the well-known effects on the gastrointestinal motility, opiates inhibit water and anion secretion over the mucosa. This effect could potentially contribute to the antidiarrheal and constipating effects of opiates. Opioids influence gastrointestinal transport via δ-receptor-mediated mechanisms. The physiological importance of this effect is unclear. Opioid modulation of motility is via the μ receptor, suggesting a functional specialization of the opioid systems in regard to motility and secretion, respectively. Recent methodological advances in the studies of neuropeptide biosynthesis offer potential applications for gastrointestinal opioid systems.
ChemInformVolume 20, Issue 51 Reviews ChemInform Abstract: Synthesis of Gastrointestinal Hormones Using Organic Chemical or Recombinant DNA Techniques N. YANAIHARA, N. YANAIHARA Lab. Bioorg. Chem., Shizuoka Coll. Pharm., Shizuoka, Jap.Search for more papers by this authorC. YANAIHARA, C. YANAIHARA Lab. Bioorg. Chem., Shizuoka Coll. Pharm., Shizuoka, Jap.Search for more papers by this author N. YANAIHARA, N. YANAIHARA Lab. Bioorg. Chem., Shizuoka Coll. Pharm., Shizuoka, Jap.Search for more papers by this authorC. YANAIHARA, C. YANAIHARA Lab. Bioorg. Chem., Shizuoka Coll. Pharm., Shizuoka, Jap.Search for more papers by this author First published: December 19, 1989 https://doi.org/10.1002/chin.198951323Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume20, Issue51December 19, 1989 RelatedInformation
Publisher Summary The radioimmunoassay (RIA) technique has been indispensable in obtaining much knowledge about both the physiology and biochemistry of gut hormones and has moreover, been crucial for diagnosing gut hormone abnormalities. One of the reasons further improvement and sophistication of RIA became necessary is the gradual recognition of a number of complex molecular characteristics for regulatory peptides in general and gut peptides in particular. These features include the molecular heterogeneity of the individual hormone, the structural homology among the groups of hormones, the widespread synthesis, that is, synthesis in many different tissues and cells, and the cell-specific processing of the precursor molecule. This chapter discusses the general aspects and the problems for RIAs of gastrointestinal hormones. It highlights the structural and biological characteristics of gut hormones. To evaluate the reliability of RIA data, careful assessment of antiserum specificity and avidity has to be performed for every RIA, because the antiserum in its reaction with the tracer governs sensitivity and specificity of the assay. Sequence-specific assays have proved such a useful way of applying the RIA technique to the study of gut hormones. Sequence-specific RIAs are panels of assays specific for different sequences of the (gut) peptides.
Dose—response characteristics of feline corpus circular muscle were studiedin vitro for three neuropeptides individually and with vasoactive intestinal peptide. Bombesin, substance P, and cholecystokinin-octapeptide each elicited concentration-dependent isometric contractions that were reduced by 10−8 M or 10−7 M vasoactive intestinal peptide (P<0.01). The concentration of each neuropeptide producing a half-maximal response was increased more than one logfold to ≥10−6 M by vasoactive intestinal peptide. Tetrodotoxin blocked responses to bombesin (P<0.001) and reduced responses to substance P (P<0.05), but had no effect on responses to cholecystokinin-octapeptide (P>0.1). These results demonstrate inhibition of neuropeptide responses of gastric smooth muscle and support vasoactive intestinal peptide as an inhibitory regulator of gastric motor function.
In summary, before hypothesizing synthesis of insulin in nonpancreatic tissues, one must determine with some accuracy the insulin concentrations in tissues such as the brain of various species or in IM-9 lymphocytes, or of non-guinea pig insulin in guinea pig tissues. If the concentrations are no more than a few percentage points of the levels initially reported by the NIH laboratory (Havrankova et al., 1978, 1979; Rosenzweig et al., 1980a,b), then some explanation should be given for the erroneously high concentrations that they earlier reported. If the very much lower concentrations that we have reported (Eng and Yalow, 1979, 1980, 1981, 1982; Bauman et al., 1982) are the true levels, then attempts to demonstrate synthesis in extrapancreatic tissues either by amino acid incorporation or by the methodology that has been described by Giddings et al. (1982) are doomed to failure. Our observations that transfer from the periphery can result in insulin levels in the brains of small-brained but not of large-brained animals comparable to or even, on occasion, higher than plasma levels when plasma levels are falling can account for our earlier observations (Eng and Yalow, 1979, 1980) that in rat but not in dog or rabbit brain insulin concentrations may be comparable to plasma levels. Furthermore, the absence of mechanisms in nonendocrine cells for the complex processing of insulin precursors to the 6000-dalton peptide and the absence of proinsulin in the extracts of the variety of tissues reported from the NIH laboratory suggest that the insulin found in these extracts was ultimately derived from pancreatic insulin.
