Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first step in the action of polypeptide hormones and many neurotransmitters is binding to receptor sites on the plasma membrane of the cell. These receptors are usually complex, high molecular weight proteins. Using a variety of receptor preparations and radioactively labeled hormones, radioreceptor assays for several hormones have been developed. These have allowed for assay of hormones for which no immunoassay exists. Such assays have shown increased levels of NSILA-s (an insulin-like peptide) in patients with nonpancreatic tumors and hypoglycemia. In disease states, the number or affinity of hormone receptors may be altered, leading to hormone resistant states such as the insulin resistance of obesity. A major factor regulating receptor concentration is the hormone itself. Several hormones seem to accelerate inactivation of their own receptors. Antibodies to membrane receptors are produced in at least three diseases and cause hormone resistance or mimic states of hormone excess.
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PMID:Receptors for peptide hormones. New insights into the pathophysiology of disease states in man. 18 59

Pancreatic Polypeptide (PP) was first described in birds by Kimmel et al. (1968). It was later isolated from the pancreas of several mammalian species by Chance and Jones (1974). It has been demonstrated in the islets of many animal species by immunocytochemical methods. PP levels are assayable in plasma and rise sharply after food intake. The pharmacological properties and physiological role of PP are still ill defined. It appears to have a spectrum of actions peculiar to each species. Recent research on this subject is reviewed in this article. High levels of circulating PP have been demonstrated in juvenile and maturity-onset diabetics, as well as in some patients with islet cell tumors. However no definite clinical syndrome due to hypersecretion of PP as been identified as yet. It remains a matter of speculation that a deficiency of PP might be responsible for some types of obesity. PP-cells are rare in the pancreas of healthy young individuals. Hyperplasia of PP-cells has been observed in a wide variety of pathological conditions, but is most prominent in the pancreas of chronic insulin dependent diabetics. Histologic evidence strongly suggests that PP-cell hyperplasia represents an atypical form of islet regeneration. It is always focal in distribution and is most remarkable in those lobules that have lost the capacity to reproduce islets of normal cytologic composition.
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PMID:[Pancreatic polypeptide (author's transl)]. 21 73

Following Yalow and Berson's basic research on the binding of polypeptide hormones to plasma proteins, an integrated picture of hormone-receptor interaction and biological activity has been proposed for insulin in experimental models and in man. The extracellular interaction of the insulin molecule with the cell membrane structure modifies the intracellular metabolism, and it has been suggested that this occurs through the activation of a second messenger or the transduction of an insulin fragment into the cell. The use of monoiodoinsulin has made it possible to perform a series of experiments on cells isolated from the blood (monocytes) or from the tissues (adipocytes) and on plasma membranes prepared by ultracentrifugation. The existence of specific receptor sites for insulin in all cases, both in animals and in man, has been confirmed by mathematical analysis of the binding curves; their non-linear course, as plotted by Scatchard's method, may depend on negative cooperation or on different classes of receptor. From an evaluation of recent studies on human obesity, particularly on adipocytes and circulating monocytes, a new approach to the problem of 'insulin resistance' in obesity has been proposed, and this has shown that a reduction in the number of receptors on the target cells may contribute to peripheral insulin insensitivity. This phenomenon, which seems to be characteristic of the static phase of obesity, is reversible during fasting or weight reduction and may be a compensatory mechanism for hyperinsulinaemia. These results are an example of the significance and applicability of the experimental method of detecting insulin binding to target cells, and suggest a wide application in different endocrinological fields.
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PMID:Insulin binding to target cells (general survey, problems and results in spontaneous obesity). 50 97

Amylin, also called islet amyloid polypeptide (IAPP), or diabetes-associated peptide (DAP) is a recently discovered 37 amino acid polypeptide which has been shown to be co-secreted with insulin from the pancreatic beta-cell. The peptide turned out to be the major constituent of pancreatic amyloid deposits which are frequently found in the pancreas of type II diabetic patients. Therefore, a role for amylin in the aetiology of type II diabetes was hypothesized. To investigate this possibility, several studies have been performed to elucidate whether amylin is able to impair insulin secretion and action, two characteristic features of type II diabetes mellitus. These studies suggest that it is unlikely that amylin has a direct inhibitory effect on insulin secretion. Amyloid deposits, however, which are derived from the in situ polymerization and precipitation of amylin, may impair beta-cell function during type II diabetes by damaging and covering beta-cells. Furthermore, it has been shown that amylin has the potential to antagonize the action of insulin on glucose metabolism by increasing hepatic glucose production and by decreasing muscle, but not adipocyte glucose uptake. For these reasons, it has been suggested that amylin might be involved in the pathophysiology of type II diabetes and obesity, disease states which are characterized by abnormal beta-cell function and insulin resistance. In addition, amylin was shown to induce hypocalcaemia by inhibiting osteoclast-mediated bone resorption in a calcitonin-like manner. Therefore, amylin is likely to be involved in both the modulation of glucose and calcium metabolism.
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PMID:Biological action of pancreatic amylin: relationship with glucose metabolism, diabetes, obesity and calcium metabolism. 140 45

Using two-dimensional electrophoresis on total extracts of adipose tissue from young lean (Fa/fa) and obese (fa/fa) Zucker rats, we have investigated the existence of early events at the protein level, before obvious obesity. Our results indicate that the two genotypes do not differ at 3 days of age in terms of polypeptide pattern. By 7 days of age, two polypeptides are transiently repressed in the fatty genotype, leading us to suggest their potential involvement in the onset of obesity. However, most of the differences between the lean and obese rats are detected at 30 days of age, characterized by an increase in the accumulation of several peptides in the adipose tissue of obese rats, in good agreement with the multiple biochemical changes previously identified at this stage of the disease. These results present evidence of new peptides that may be of interest in the study of the obesity syndrome.
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PMID:Differential polypeptide expression in adipose tissue of lean and obese Zucker rats. Evidence of specifically repressed peptides in 7-day-old pre-obese rats. 162 98

The effects of oral diethylaminoethyl-dextran (3 g total), taken 30 min before a standard mixed test meal, on plasma glucose, total cholesterol, triglycerides, total lipids, gastrin-like immunoreactivity, bombesin-like immunoreactivity, gastric-inhibitory-polypeptide-like immunoreactivity and neurotensin-like immunoreactivity were evaluated in eight healthy volunteers following a double-blind protocol. Incremental peak plasma concentrations of total lipids and triglycerides were significantly reduced by pretreatment with diethylaminoethyl-dextran pretreatment, while peaks of plasma glucose and total cholesterol were not significantly affected. Diethylaminoethyl-dextran also inhibited postprandial gastrin-like gastric-inhibitory-polypeptide-like and neurotensin-like immunoreactivity; by contrast, bombesin-like immunoreactivity was not significantly modified. The present study indicates that diethylaminoethyl-dextran is able to regulate some postprandial metabolic and hormonal parameters in man; consequently it might be useful in the treatment of hyperlipoproteinaemia and obesity.
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PMID:Short-term effects of diethylaminoethyl-dextran on postprandial gastrointestinal hormone responses in man. 169 37

Amylin, a 37-amino acid polypeptide, has been identified as the major protein component of pancreatic amyloid deposits in patients with non-insulin-dependent (type II) diabetes mellitus. Amylin is stored and released together with insulin and has been proposed to play a major role in the pathogenesis of type II diabetes. To compare amylin release and its proportion to insulin secretion under different metabolic conditions, oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in healthy, lean control subjects, obese patients with normal and impaired glucose tolerance (NGT and IGT, respectively), and obese type II diabetic patients. Compared with control subjects, basal and stimulated amylin secretion during OGTT was significantly higher in obese patients with NGT and IGT but not in type II diabetic patients. The integrated amylin response was significantly higher in obese patients with NGT than lean control subjects and type II diabetic patients matched for degree of obesity. The amylin-insulin ratio decreased slightly in obese subjects with NGT and IGT and significantly in type II diabetic patients. Amylin secretion was significantly stimulated during IVGTT in control subjects and obese patients with NGT and IGT but not in type II diabetic patients. These findings suggest that amylin is physiologically released by pancreatic beta-cells in a constant ratio to insulin in nondiabetic subjects. Glucose-stimulated amylin secretion is increased in obese subjects with NGT and IGT. In type II diabetes mellitus, amylin secretion relative to that of insulin is decreased, and amylin is not stimulated by IVGTT.
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PMID:Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes. 175 2

A homeomorphic mathematical model of cell surface insulin receptor regulation is developed. The overall structure of the model is based on molecular mechanisms suggested by in vivo and in vitro experimental evidence from many different cell types. Model parameters correspond to cellular processes which are constrained by known boundry value conditions. As an example, computer simulation results are compared with published data from BC3H-1 myocytes in culture. With appropriate parameter choice, this model is able to simulate data from other cell types. Cellular processes which are explicitly represented in the model include: bound and unbound receptor endocytosis, receptor recycling, intracellular receptor degradation, and state-dependent receptor synthesis. Most of these processes are represented as first-order events. Using more complex representations of the model structure with higher order rate constants or saturable pathways does not qualitatively improve simulation results. Simulations are able to reproduce ligand-induced down and up regulation of receptors as well as the initial spontaneous display of surface insulin receptors. To demonstrate the behavior of our model and illustrate its utility for explaining insulin receptor regulation for a variety of conditions, simulations for which experimental data is unavailable for direct comparison are also shown. We believe the structure of our model is sufficient to explain insulin receptor regulation in a wide variety of cell types. In addition our model may aid in understanding the receptor component of insulin resistance (decreased sensitivity or responsiveness to insulin) seen in pathological states such as obesity and diabetes mellitus. Finally, this model may be applicable to the study of the regulation of other polypeptide hormone receptors.
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PMID:A mathematical model and computer simulation study of insulin receptor regulation. 189 Aug 48

We have shown in earlier studies, that the development of spontaneous autoimmune thyroiditis (SAT) in chickens of the Obese strain (OS) depends on the presence of both, two dominant genes coding for an altered immune regulation and one recessive gene responsible for the susceptibility of the target organ for the autoimmune attack. The product(s) of the latter is (are) still not known. The present study was aimed at identifying possible candidates of cellular components of the thyroid gland of OS chicken and its SAT susceptible parental Cornell C-strain (CS) by high resolution 2-dimensional (2D) gel electrophoresis. For this purpose organ cultures of the thyroid, bursa, thymus and liver were established and the synthesized polypeptides were labelled by 35S-methionine. OS and CS organs were compared with those of healthy normal White Leghorn (NWL) controls. The autoradiographs of the 2D-gels obtained from individual samples after various labelling periods were subjected to comparative analysis. We have found both quantitative and qualitative differences of polypeptide spots between OS/CS and NWL organ samples, some of them specific for the thyroid gland. Although one has to be aware that in this multidimensional analytical approach numerous, still elusive pattern differences are revealed, the thyroid specific phenomena will be further scrutinized.
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PMID:Molecular analysis of genetically determined target organ abnormalities in spontaneous autoimmune thyroiditis. 209 9

beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D-glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta-lipotropin.
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PMID:Processing of the lipid-mobilizing peptide beta-lipotropin in rabbit adipose tissue. 221 32


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