Incretin effect in prediabetic subjects Seyyed Mohammad Gheibi Hayat. Peptide hormones as regulators of glucose homeostasis Lynda Whiting. The contribution of incretin hormones to the pathogenesis of type 2 diabetes. Juris J Meier. Nutrient-induced secretion and metabolic effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide Jacqueline M.
Interaction of caerulein, glucose, and amino acids on insulin secretion from the perfused rat pancreas. Gastric inhibitory polypeptide GIP. References Publications referenced by this paper. Hormones of the gastrointestinal tract. Stephen Robert Bloom. Radioimmunoassay for gastric inhibitory polypeptide.
Release of gastric inhibitory polypeptide: comparison of glucose and fat as stimuli. Not registered? Create account My Content 1 Recently viewed 1 Characterization of ra Authors: S. Sharma , C. Austin , A.
Howard , G. Nicholl and S. Restricted access. Check for updates. Related Articles. Hence, they are truly different hormones. Hence, in some animals, proglucagon delivers two different gut hormones. Proglucagon tells another story of general interest. Deduction of its structure from cloned cDNA provided, in the case of preproglucagon, the first evidence or suggestion of separate bioactive peptide moieties from the same precursor due to the striking homologies between the sequences 33—61 pancreatic glucagon , 72— the original GLP-I , and — GLP-II 15 Physiological studies showed, however, that the first deduced and proposed GLP-I proglucagon 72— , which is situated between two dibasic sites in the precursor, is a poorly active peptide Instead, a truncated form of the original GLP-I, which corresponds to the proglucagon sequence 78—, turned out to be a highly potent glucoregulatory peptide Moreover, it is the shorter fragment 78— that is synthesized and secreted in the gut and that therefore is the genuine GLP-I hormone.
The New Biology of Gastrointestinal Hormones
The lesson of this story is, consequently, that bioactive peptide structures cannot be predicted from cDNA and precursor sequences. It requires also precise identification of the released peptides accompanied by proper physiological studies of their activities. The term gene expression is widely used. Unfortunately, however, it is also broad and is often used in an unspecific manner. Sometimes it refers only to demonstration of mRNA molecules, irrespective of whether the message is translated or not. On other occasions, it refers to synthesis of the primary translational product, irrespective of whether the protein product is processed to a functionally active form.
Finally, it may be used in a more phenotypic sense to indicate the presence of the protein or peptide in its bioactive form, i. For gastrointestinal hormones and other regulatory peptides, the expression cascade is generally highly elaborate and involves multiple enzymatic steps. Each of these steps may control whether the initial transcription process in the end results in a bioactive product. It is in fact not unusual to see gene transcription without the encoded bioactive end product.
Accordingly, reports on lack of parallelism and synchrony between the occurrence of mRNA, propeptide, and the mature bioactive peptide are steadily increasing for review, see Ref. Especially in a physiological context, it becomes important to know whether transcription results in a bioactive product. Otherwise, what, for instance, is the physiological significance of the abundant but untranslated secretin mRNA in the colorectal mucosa ; Table 5? In other words, it is not possible to conclude that mRNA occurrence means synthesis of functionally active peptides.
Table 4. Expression of procholecystokinin and its products in mammalian tissue. Orders of magnitude are based on examination of different mammalian species in the laboratory of the author 79 F Cholecystokinin peptides are present in spermatozoa of nonhuman mammals. The concentration, however, has not been quantitated.
Table 5. Expression of secretin peptide and mRNA in mammalian tissue. Orders of magnitude are based on examination of different mammalian species All gut hormones are widely expressed in tissues outside the gastrointestinal tract, also phenotypically in terms of bioactive peptides. For some, the extraintestinal expression is confined mainly to neuroendocrine cells, especially to neurons in the central and peripheral nervous systems. However, several gastrointestinal hormones are expressed also in other cell types and tissues Tables The literature on extraintestinal expression of gut hormones is by now overwhelming.
Therefore, the phenomenon will be illustrated with two examples only, namely, gastrin and CCK. Also, only sites of expression will be mentioned where proper gastrin or CCK peptides have been demonstrated. The gastrin gene expression occurs widely and promiscuously in many different cell types, whereas CCK exemplifies extraintestinal expression restricted to neuroendocrine cells.
Gastric inhibitory polypeptide - Wikipedia
The gastrin gene is as mentioned expressed at the peptide level in several other cell types than the antroduodenal G cells. Quantitatively, these other cells produce only little of the gastrin released to blood in normal organisms. This is partly because the extra-antral secretion seems to serve local purposes rather than a general endocrine purpose, and partly because the biosynthetic processing often is cell specific, i. So far, we have encountered expression of progastrin and its products outside antroduodenal mucosa in the distal small intestine, perhaps originating from the so-called TG cells 37 79 ; in unidentified cells in the colorectal mucosa ; in endocrine cells in the fetal and neonatal pancreas 10 26 ; in pituitary corticotrophs and melanotrophs ; in oxytocinergic hypothalamopituitary neurons ; in a few cerebellar and vagal neurons ; in the adrenal medulla of some species unpublished results ; in the bronchial mucosa ; in postmenopausal ovaria ; and in human spermatogenic cells The precise function of gastrin synthesized outside the antroduodenal mucosa is unknown, but several suggestions can be offered.
First, an obvious possibility is local paracrine or autocrine regulation of growth. Second, it is possible that the low concentration of peptides is without significant function in the adult but is a relic of a more comprehensive fetal synthesis meant for local stimulation of growth 10 A third possibility is that the low cellular concentration is due to constitutive rather than regulated secretion With constitutive secretion, there is no storage of peptides in the cells in spite of a considerable release per time unit.
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However, clues to the significance of extra-antral gastrin are still lacking and awaiting further studies of double and triple knock-out mice. The CCK gene is expressed at the peptide level in several other cell types than the small intestinal I cells. However, in contrast to the homologous gastrin gene, CCK gene expression is confined to neuroendocrine cells Table 4 of which CCK neurons in the brain predominate.
Neurons in all regions of the central nervous system synthesize carboxyamidated CCK peptides, although cerebellar neurons only in the fetal state The highest expression occurs in neocortical regions, which explains why CCK is the most abundant peptide system in the mammalian brain 52 Cholecystokinin peptides are also widely expressed in peripheral neurons, primarily in the intestinal tract, but also in the genitourinary tract and elsewhere Low-level expression has been found in pituitary corticotrophs , in thyroid C cells , in the adrenal medulla 9 , in the bronchial mucosa 86 , and in spermatogenic cells of certain species Although neuronal CCK peptides act as potent transmitters in central and peripheral synapses, the roles, if any, of CCK peptides in pituitary, thyroid, and adrenal endocrine cells are unknown.
Neuronal CCK peptides seem to play decisive roles in the development of anxiety and panic disorders in humans and other mammals 23 — 25 as well as some role in satiety disorders 87 The exact molecular and neuronal mechanisms in these disturbances remain to be clarified. A striking difference in the cellular expression of the otherwise homologous gastrin and CCK genes 57 is the high degree of promiscuity in the expression of the gastrin gene.
Cholecystokinin peptides are, with the exception of germ cells , apparently never synthesized outside endocrine cells or neurons. Also, when it comes to neoplasia, benign as well as malignant, CCK peptides only occur in tumors of neuroendocrine origin for review, see Ref. In contrast, gastrin peptides are synthesized in many other types of cells than neuroendocrine, and this feature becomes further prominent in tumors Hence, gastrins have been found not only in the relatively rare neuroendocrine tumors but also in significant amounts in common carcinomas such as bronchogenic, colorectal, gastric, pancreatic, and ovarian cancers 48 89 — ; for review, see Ref.
Interestingly, local expression of the gastrin receptor seems to accompany the widespread expression of gastrin peptides in cancers Schematic illustration of cell-specific processing of preprogastrin in antral G cells see also Fig. The definitive molecular explanation s of the different extraintestinal expression patterns for CCK, gastrin, and other gut hormones remains to be found.
Part of the explanation will have to be sought in the transcriptional regulation. Accordingly, the promoters of the otherwise homologous gastrin and CCK genes display marked differences in number and types of regulatory sites.