The possible role of the gut neuroendocrine system in diabetes gastroenteropathy

Gastrointestinal symptoms such as nausea and vomiting, heartburn, abdominal pain, diarrhoea, constipation and faecal incontinence are common in patients with diabetes. Diabetes gastroenteropathy is a clinically relevant problem. In addition to the increased morbidity it causes, it results in severely impaired metabolic control, which in turn increases the risk of hyper-/hypoglycaemia. Moreover, the poorly controlled blood glucose level increases the risk of secondary diabetes complications, namely, retinopathy, nephropathy, neuropathy and cardiovascular affection. Gastrointestinal symptoms may also cause malnutrition in patients with diabetes, which, together with the disturbed immune defence in diabetes, may cause intercurrent infections. Gastrointestinal symptoms in patients with diabetes are attributed to disturbed gastrointestinal motility. Gastrointestinal dysmotility in diabetes is believed to be caused by autonomic neuropathy and/or hyperglycaemia. The neuroendocrine system of the gut secretes peptides/amines that play an important role in regulating gastrointestinal motility. It is conceivable, therefore, to assume that a disturbance in this regulatory system may contribute to the pathogenesis of gastrointestinal complications in diabetes. The present review gives an updated overview of the abnormalities in the gastrointestinal neuroendocrine system in diabetes, speculates upon the possible role of these abnormalities in the pathogenesis of diabetes gastroenteropathy and, finally, predicts the possible clinical implications of these findings.     

Muscular system in polychaetes (Annelida)

The structure of the polychaete muscular system is reviewed. The muscular system comprises the muscles of the body wall, the musculature of the parapodial complex and the muscle system of the dissepiments and mesenteries. Various types of organisation of the longitudinal and circular components of the muscular body wall are distinguished. In Opheliidae, Polygordiidae, Protodrilidae, Spionidae, Oweniidae, Aphroditidae, Acoetidae (=Polyodontidae), Polynoidae, Sigalonidae, Phyllodocidae, Nephtyidae, Pisionidae, and Nerillidae circular muscles are lacking. It is hypothesised that the absence of circular muscles represents the plesiomorphic state in Annelida. This view contradicts the widely accepted idea of an earthworm-like musculature of the body wall comprising an outer layer of circular and an inner layer of longitudinal fibres. A classification of the various types of parapodial muscle construction has been developed. Massive and less manoeuvrable parapodia composed of many components like those of Aphrodita are regarded to represent the plesiomorphic state in recent polychaetes. An analysis of the diversity of the muscular structure supports the hypothesis that the primary mode of life in polychaetes was epibenthic and the parapodial chaetae had a protective function.     

The infracerebral gland--a possible neuroendocrine complex in Nereis

The infracerebral gland of Nereis consists of an epithelium covering the ventral surface of the posterior region of the brain. The thickness of the epithelium varies greatly in different species, and it appears especially well developed in Nereis limnicola. Cells of the most numerous type are in direct contact with the base of the brain. Their apical surfaces bound a coelomic sinus, below which is a blood plexus. Other cells are fuchsinophilic and contain many inclusions resembling elementary neurosecretory granules. A third type is rare and resembles glial elements. A number of nerve tracts run from the neuropil to the base of the brain in the region of the gland. Where they impinge upon the capsule they form swellings containing elementary granules and small vesicles. Some axons do not end on the capsule but pass through the capsule and then ramify among the cells of the gland. The swollen endings of other fibers, probably nervous in character, are packed with mitochondria and are scattered over the inner surface of the capsule in the region of the gland. The features described are suggestive of a neuroendocrine complex, and the relation between the brain and the infracerebral gland is in need of experimental analysis in view of the important endocrine functions presently ascribed to the brain in nereids.     

Diversity of reproductive features in some Antarctic polynoid and sabellid polychaetes, with a description of Demonax polarsterni sp. n. (Polychaeta, Sabellidae)

The Polynoidae and Sabellidae represent two polychaete families with contrasting life habits and different phylogenetic constraints. Species of both families studied in this work were collected on the shelf of the Eastern Weddell Sea (Antarctica) during the EASIZ-I (1996) and EASIZ-II (1998) expeditions. Among the Polynoidae, three different species of the genus Harmothoe were observed to brood eggs under the dorsal elytra, which is an uncommon feature in this family. The egg size of all brooding taxa ranged between 120 and 216 µm. Three Sabellidae species were studied: Myxicola cf sulcata is gonochoric with eggs among the largest (up to 1000 µm) recorded for the sabellids. Eggs, as well as larvae, are incubated within the branchial crown, a feature newly discovered for the genus Myxicola. Demonax polarsterni n. sp. (a newly discovered taxon) and Euchone pallida are gonochoric and possess relatively large eggs (350 µm and 270 µm, respectively). In comparison with cogeneric species of temperate areas, the Antarctic Sabellidae have larger egg dimensions and egg brooding that seems unconstrained by adult size.     

A study of fighting reactions in some nereid polychaetes

Fighting reactions have been studied in three nereid polychaetes. Fighting occurs less often in intra- than inter-specific encounters. Many intra-specific encounters end without fighting because the worms either separate immediately on contact, or explore one another with their palps and then separate. Individual Nereis pelagica can discriminate between individuals of their own and foreign species because they react differently in intra- and inter-specific encounters. After removal of any one of the anterior sense organs (cirri, palps or tentacles), they can still make this discrimination but cannot do so after removal of all three of these sense organs.     

The immune system in neuroendocrine tumors

During the last 30 years the incidence of neuroendocrine tumors has increased considerably and the overall 5-year survival rate has not changed substantially. Conventional therapeutic approaches appear to show an unsatisfactory effect in the more insidious forms of malignancies. Hence, attempts were made to direct the patient's own immune system against cancer by vaccinating against different tumor antigens. Up to date, only sporadic achievements were demonstrated in the majority cases of vaccination trials. One of the main hindrances to a successful vaccination comprises tumor-immune-escape mechanisms. This review focuses on the current knowledge concerning tumor immunoevasion strategies and the immune system in neuroendocrine tumors.     

The ventricular system in neuroendocrine mechanisms

Summary This investigation has utilized a correlative scanning-transmission electron microscopic technique in the analysis of the primate cerebral ventricular system. This approach has demonstrated a complex network of supraependymal cellular elements upon the walls of the third cerebral ventricle in direct contact with the ventricular lumen. Type I neuronal-like cells and type II histiocytic-like cells with potential phagocytic capabilities have been observed in large numbers throughout the third ventricle. Type I neuron-like cells are discussed in the context that they may represent a population of receptor-cells which serve to assess ambient changes in the composition of bioactive peptides in the cerebrospinal fluid and may serve as a supraependymal network that integrates the endocrine hypothalamus with other circumventricular organs which may also be sites of neuroendocrine transduction.Supported by USPHS Program Project Grant NS-11642Career Development Awardee GM K04 70001     

Cladistics and polychaetes

A series of cladistic analyses assesses the status and membership of the taxon Polychaeta. The available literature, and a review by Fauchald & Rouse (1997), on the 80 accepted families of the Polychaeta are used to develop characters and data matrices. As well as the polychaete families, non-polychaete taxa, such as the Echiura, Euarthropoda, Onychophora, Pogonophora (as Frenulata and Vestimentifera), Clitellata, Aeolosomatidae and Potamodrilidae, are included in the analyses. All trees are rooted using the Sipuncula as outgroup. Characters are based on features (where present) such as the prostomium, peristomium, antennae, palps, nuchal organs, parapodia, stomodaeum, segmental organ structure and distribution, circulation and chaetae. A number of analyses are performed, involving different ways of coding and weighting the characters, as well as the number of taxa included. Transformation series are provided for several of these analyses. One of the analyses is chosen to provide a new classification. The Annelida is found to be monophyletic, though weakly supported, and comprises the Clitellata and Polychaeta. The Polychaeta is monophyletic only if taxa such as the Pogonophora, Aeolosomatidae and Potamodrilidae are included and is also weakly supported. The Pogonophora is reduced to the rank of family within the Polychaeta and reverts to the name Siboglinidae Caullery, 1914. The new classification does not use Linnaean categories, and the Polychaeta comprises two clades, the Scolecida and Palpata. The Palpata has the clades Aciculata and Canalipalpata. The Aciculata contains the Phyllodocida and Eunicida. The Canalipalpata has three clades; the Sabellida (including the Siboglinidae) Spionida and Terebellida. The position of a number of families requires further investigation.     

Swimming mechanisms in nereidiform polychaetes

New observations of the swimming of several species of nereidiform polychaete are presented and the parameters of body motion analysed. It is shown that there are theoretical limits to the values of these parameters outside which propulsion by the wave motion of the body is impossible. Many of the observations do fall outside them. This is because of the effect of the beating parapodia. Kinematic considerations are introduced to show how the wave of parapodial activity is related to the wave motion of the body. Dynamic considerations lead to an estimate of the minimum Young's modulus of the parapodia for pure parapodial swimming, lower values being possible for a combination of body-wave and parapodial swimming. The speeds achieved by different methods of swimming are discussed for the species that have been examined.     

Thymulin and the neuroendocrine system

Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to this molecule. After its discovery in the early 1970, thymulin was characterized as a thymic hormone involved in several aspects of intra- and extrathymic T-cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, an emerging core of information points to thymulin as a hypophysotropic peptide. Here we review the evidence supporting the hypothesis that thymulin is an important player in the hypophyso-thymic axis.     

The fine structure of neuroglia in the central nervous system of nereid polychaetes

Summary The principal supportive elements of the nereid central nervous system are non-neuronal cells that are referred to as supportive glia. Supportive glial cells form a conspicuous cortex in the nerve cord. The inner region of this cortex consists of closely packed processes and cell bodies of fibrous supportive glial cells that are arranged in concentric layers around the perimeter of the neuropile. The fibrous appearance of the glial cells results from dense bundles of cytoplasmic filaments. Many fibrous glial processes penetrate the neuropile and ramify among the neuronal elements. Larger, irregularly shaped cells are the chief supportive glial elements of the peripheral region of the cortex where they line the stromal sheath (neural lamella) and invest the neuronal perikarya with extensive concentric systems of lamellate processes. These glial cells usually possess a relatively undifferentiated cytoplasm with scattered glycogen granules, but occasionally have a well developed Golgi apparatus, endoplasmic reticulum and densely packed particulate glycogen. The supportive glia exhibits numerous desmosomes as well as 5-layered (tight) and 7-layered (gap) junctions. Interspersed among the supportive glial cells are non-neuronal cells referred to as granulocytes. These cells have abundant large, granular inclusions, electron lucent vesicles, plasmalemmal infoldings and microtubules. The granulocytes may be derived from undifferentiated glial cells or may represent coelomocytes that have invaded the nervous tissue.Supported by USPHS Grants No. NIH 5P01 NS-07512, NIH 2T01 GM-00102, and NB-00840.The author acknowledges the excellent technical assistance of Sarah Wurzelmann and Stanley Brown, and thanks Dr. Berta Scharrer for many stimulating discussions.     

Role of the neuroendocrine system in aging

The study involves 3 aspects of neuroendocrine control over the organism functions in aging: the decline in reproductive functions, the reduction of growth hormone secretion and the decrease in thymic functional activity and the altered relationship between neuroendocrine and immune systems. The role that an age-related decrease in dopamine and noradrenaline production by hypothalamic neurones plays in the above age changes in neuroendocrine control has been traced. The age-related decrease in functions of hypothalamic catecholaminergic neurones is apparently caused by the damaging effect of hormones (prolactin, glucocorticoids and, especially, estrogen), free radicals and toxins, both of the endogenous and exogenous origin. The restrained nutrition increases lifespan of the experimental animal owing to reduced "wear out" of the neuroendocrine system and organs and tissues that are controlled by this system.     

Morpho-functional principle of neuroendocrine system analysis

A new approach to the analysis of the neuroendocrine system (NES) is suggested. It is based on the fact of structural and metabolic determination of any effect on cell and cell aggregates. The principle of a common communication channel in the NES is formulated and a possible method of its formalization is proposed.     

Formation of diffuse neuroendocrine system in human ontogenesis

The review of literature presents data on formation of the diffuse neuroendocrine system (DNES) in human early ontogenesis and its role in development of organs and vitally important functional systems of the fetus. It is emphasized that impairment of structural development and/or changes of the functional state of DNES cells under effects of unfavorable environmental factors can underlie embryopathies, fetopathies, and disorders of early postnatal adaptations of children.     

FMRF-amide immunoreactivity in the mammalian gastroenteropancreatic neuroendocrine system

Summary The presence of FMRF-amide, a cardioactiv tetrapeptide, was studied by immunocytochemistry in human and rat gastric antrum and pancreas, and in the ovine, bovine, canine and rabbit pancreas. In human and rat gastric antrum, numerous cells contained FMRF-amide immunoreactive material. By staining of serial sections and by double staining, colocalization of immunoreactivity for gastrin and FMRF-amide was observed in part of the gastrin cells. In the pancreas of these and the other species, immunoreactivity for FMRF-amide was located both in acinar and islet endocrine cells. Colocalization of FMRF-amide and pancreatic polypeptide was found in a proportion of pancreatic polypeptide cells in the pancreas. FMRF-amide immunoreactivity never colocalized with the other neurohormonal peptides which occur in the gastric antrum and the pancreas.Our observations show that neuroendocrine cells occur in the gastric antrum and pancreas which are exclusively immunoreactive or gastrin and for pancreatic polypeptide respectively. In addition cells occur which show immunoreactivity for FMRF-amide as well as for gastrin in the gastric antrum and with antiserum to FMRF-amide as well as for pancreatic polypeptide in the pancreas. It is concluded that FMRF-amide antibodies probably recognize a substance in G and PP cells which is not identical but may be structurally related to gastrin and pancreatic polypeptide.In honour of Prof. P. van Duijn