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)

Pseudohypoparathyroidism is a condition in which for some reason the normal effect of PTH in the target organ fails to occur. In the Ia type here described the signal transmission is impaired due to abnormal genetic development of the stimulating G protein (Gs) in the cell membrane resulting in insufficient cAMP production after binding of PTH on the membrane receptor. The failure to occur of the normal PTH effect impairs the calcium homeostasis. In many cases this type of pseudohypoparathyroidism is associated with phenotypical characteristics such as short stature, round face, obesity, brachydactyly, subcutaneous and intracerebral calcifications and sometimes bradyphrenia. Since the Gs protein aspecifically also brings about production of cAMP after binding of other polypeptide hormones to this hormone-specific receptor, several hormone resistances may be present concurrently.
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PMID:[Pseudohypoparathyroidism; where is the hitch?]. 224 48

The concentrations and contents of immunoreactive substance P (SP), neurokinin A (NKA), vasoactive intestinal polypeptide (VIP) and gastrin releasing peptide (GRP) were measured in acid-ethanol extracts of intestine (duodenum-jejunum-ileum) and pancreas of C57BL/KsJ diabetes-obese (db/db) mice, Aston obese-hyperglycaemic (ob/ob) mice, and their respective lean controls. The intestinal concentration of GRP and pancreatic concentrations of VIP and GRP were 36-57% lower in lean Aston mice than lean C57BL/KsJ mice, indicating the influence of genetic background in control mice. Intestinal concentrations of SP and NKA were reduced by 19-33% in the db/db and ob/ob mutants compared with their lean controls, but the intestinal contents of these peptides were normal or greater than normal due to intestinal hypertrophy of the mutant mice. The intestinal VIP concentration was not altered, but the content was increased by 87% and 25% respectively in db/db and ob/ob mice, whereas the intestinal GRP concentration was reduced by 51% in ob/ob mice. Pancreatic concentrations and contents of NKA, VIP and GRP were similar in lean and db/db C57BL/KsJ mice. However, pancreatic concentrations and contents of VIP and GRP were reduced by 51-55% in ob/ob mice compared with their lean controls. The sensitivity of the present assay did not permit accurate determination of the low pancreatic concentrations of SP. The results suggest that the spontaneous ob/ob and db/db syndromes of obesity and diabetes in mice are associated with reduced intestinal concentrations of SP and NKA. The ob/ob mouse also exhibited reductions of intestinal GRP and pancreatic GRP and VIP concentrations. These changes in regulatory peptides may relate to abnormalities of intestinal and possibly pancreatic function in obese and diabetic mutant mice.
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PMID:Substance P, neurokinin A, vasoactive intestinal polypeptide and gastrin releasing peptide in the intestine and pancreas of spontaneously obese-diabetic mice. 243 55

Ten obese and 10 control subjects were studied in basal conditions and after ingestion of a standard mixed test meal. Blood glucose, insulin, somatostatin (SLI) and vasoactive intestinal polypeptide (VIP) concentrations were determined before and 30, 60, 90, 120, 180 and 240 min after the start of the meal. Basal SLI levels in the obese (14.4 +/- 0.7 ng/l) were not significantly different from those in the controls (15.5 +/- 0.8 ng/l), whereas after the meal a blunted secretory response was recorded. Baseline plasma VIP levels were higher in the obese (29.7 +/- 1.5 ng/l) than in the control subjects (19.8 +/- 1.3 ng/l) and, similarly to the controls, were unaffected by meal ingestion. Data suggest that in the course of obesity an enhanced VIP secretion in association with a diminished SLI responsiveness to meals occurs.
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PMID:Plasma somatostatin and vasoactive intestinal polypeptide responses to an oral mixed test meal in obese patients. 257 74

Considerable disagreement exists regarding the levels of immunoreactive glucose dependent insulinotropic polypeptide in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Glucose dependent insulinotropic polypeptide levels were therefore studied during oral glucose and mixed meal tolerance tests in normal subjects (n = 31) and newly presenting previously untreated patients with Type 2 diabetes mellitus (n = 68). The tests were performed in random order after overnight fasts and blood samples were taken at 30 min intervals for 4 h. During the oral glucose tolerance test plasma glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a fasting value of 20 +/- 3 pmol/l to a peak of 68 +/- 5 pmol/l at 30 min and in the Type 2 diabetic patients from a similar fasting level of 27 +/- 3 pmol/l to a higher peak value of 104 +/- 6 pmol/l at 30 min (p less than 0.001). Glucose dependent insulinotropic polypeptide levels were significantly higher in the diabetic patients compared with the normal subjects from 30-90 min (p less than 0.01-0.001) following oral glucose. During the meal tolerance test glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a pre-prandial value of 22 +/- 4 pmol/l to a peak of 93 +/- 6 pmol/l at 90 min and in the Type 2 diabetic patients from a similar basal level of 25 +/- 2 pmol/l to a higher peak of 133 +/- 7 pmol/l at 60 min. Glucose dependent insulinotropic polypeptide concentrations were significantly higher in Type 2 diabetic patients compared with the normal subjects at 30 min (p less than 0.001), 60 min (p less than 0.01) and from 210-240 min (p less than 0.05) during the meal tolerance test. The groups were subdivided on the basis of degree of obesity and glucose dependent insulinotropic polypeptide concentrations were still higher in the diabetic subgroups compared with the normal subjects matched for weight. Type 2 diabetes mellitus is associated with an exaggerated glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals which is independent of any effect of obesity.
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PMID:The glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals is increased in patients with type 2 (non-insulin-dependent) diabetes mellitus. 267 68

Amylin, the major peptide component of the islet amyloid commonly found in the pancreases of patients with type 2 (non-insulin-dependent) diabetes mellitus (NIDDM), is a recently discovered islet polypeptide. This peptide has many structural and functional features suggesting that it is a novel hormone, which may control carbohydrate metabolism in partnership with insulin and other glucoregulatory factors. Amylin is synthesised in, and probably secreted from, the beta-cells of the islets of Langerhans, where it has recently been immunolocalised to secretory granules. DNA cloning studies indicate that in the human and the rat, amylin is generated from a precursor, preproamylin, which displays a typical signal peptide followed by a small prohormone-like sequence containing the amylin sequence. The presence of the signal peptide suggests that amylin is secreted and plays a physiological role. Amylin is probably generated by proteolytic processing similar to that for proinsulin and other islet prohormones. The human amylin gene encodes the complete polypeptide precursor in two exons which are separated by an intron of approx. 5 kb, and is located on chromosome 12. Amylin is a potent modulator of glycogen synthesis and glucose uptake in skeletal muscle, and is capable of inducing an insulin-resistant state in this tissue in vitro, and perhaps also in the liver in vivo. In normal metabolism, amylin could act in concert with insulin as a signal for the body to switch the site of carbohydrate disposal from glycogen to longer-term stores in adipose tissue, by making skeletal muscle relatively insulin-resistant, whilst at the same time leaving rates of insulin-stimulated carbohydrate metabolism in adipose tissue unaltered. Several lines of evidence now implicate elevated amylin levels in the pathogenic mechanisms underlying NIDDM, and suggest to us that the obesity which frequently accompanies this syndrome is a result of, rather than a risk factor for, NIDDM. Following the beta-cell destruction which occurs in type 1 (insulin-dependent) diabetes mellitus (IDDM), it is probable that amylin secretion disappears in addition to that of insulin. As patients with insulin-treated IDDM frequently experience problems with hypoglycaemia, and as amylin acts to modulate the action of insulin in various tissues, it is possible that amylin deficiency may contribute to morbidity in insulin-treated IDDM, perhaps through the loss of a natural damping mechanism which guards against hypoglycaemia under conditions of normal physiology.
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PMID:Amylin and the amylin gene: structure, function and relationship to islet amyloid and to diabetes mellitus. 269 Sep 58

Somatostatin is present in the gastrointestinal tract in appreciable amounts. The highest concentrations of the polypeptide are found in the stomach, the upper small intestine, and the pancreas. Within the gastrointestinal tract, somatostatin inhibits various functions, including endocrine and exocrine secretion, motility, blood flow, absorption, and growth. The polypeptide regulates these functions by endocrine, paracrine, neurocrine or luminal mechanisms. Abnormalities of endogenous somatostatin have been implicated in several gastrointestinal disorders, including the somatostatinoma syndrome, antroduodenal D-cell hyperplasia, peptic ulcer, obesity, and liver cirrhosis. Because of its potent inhibitory effects, somatostatin or somatostatin-analogues have been used as therapeutic agents in various clinical conditions, such as upper gastrointestinal haemorrhage, endocrine pancreatic tumours, gastrointestinal and pancreatic fistulas, pancreatitis, secretory diarrhoea, and dumping syndrome. The recent availability of the synthetic long-acting somatostatin-analogue SMS 201-995 (Sandostatin) has greatly facilitated the therapeutical application of somatostatin-polypeptides.
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PMID:Clinical and pathophysiological aspects of somatostatin and the gastrointestinal tract. 289 34

Possible involvement of an endogenous digitalislike substance (EDLS) in blood pressure regulation was investigated using a Japanese population. Mean arterial pressure (MAP) significantly correlated with urinary excretion of the EDLS, age, and the obesity index. The plasma EDLS correlated with urinary EDLS. Urinary EDLS excretion well correlated with the inhibitory activity on Na+,K+-ATPase, and also with the urinary excretion of NaCl. Obesity index correlated with the Na+,K+-ATPase inhibition and arterial pressure. Although plasma content of atrial natriuretic polypeptide correlated with the urinary Na+,K+-ATPase inhibition, it did not correlate with the rest of all parameters. Plasma vasopressin level did not correlate with these parameters either. These results clearly indicate that the circulating EDLS (ie, Na+,K+-ATPase inhibitor) is implicated in the hypertension associated with an excess intake of sodium, aging and obesity.
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PMID:Endogenous digitalislike substance in an adult population in Japan. 341 95

Some decades ago clinicians accepted that, for a given height and weight, the amount of calories necessary to maintain a constant weight differed from one individual to another. There was no apparent explanation for these individual differences. Later, however, obesity was thought to be the consequence of overfeeding. We now know that in the obese subject diet-induced thermogenesis may be diminished. In the rodent, diet-induced thermogenesis occurs in brown adipose tissue and is triggered by thermogenine, a polypeptide which uncouples oxidative phosphorylation. It is probable that diet-induced thermogenesis in man is under the control of the autonomous nervous system and is probably also triggered by thermogenine. These new insights into the pathogenesis of obesity have as yet no therapeutic implications. The indications for weight reduction are discussed.
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PMID:[Old and new aspects of obesity]. 372 6

There is evidence for involvement of gastrointestinal hormones in pathogenesis of obesity and reports on lipolytic activity in animals. The in vitro lipolytic activity of these hormones was tested in human adipocytes. Vasoactive intestinal polypeptide, glucagon, secretin, human gastrin I, gastrin releasing polypeptide, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, bombesin, neurotensin, C-peptide, as well as cholecystokinin did not stimulate lipolysis significantly above basal. These results indicate that the involvement of these hormones in obesity in man might not be due to a direct lipolytic effect on the human adipocyte.
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PMID:Glycerol release from incubated human adipocytes is not affected by gastrointestinal peptides. 401 16

Identification of the fundamental polypeptide difference between yellow (A(y)/-, A(vy)/-) and non-yellow mice is important for biomedical research because of the influence of the yellow genotype on normal and neoplastic growth and obesity. The complexity of the "yellow mouse syndrome" makes attainment of this objective dependent on the separation of those pleiotropic enzyme differences which are secondary, and depend on the background genome, from those which are primary, and depend primarily on the agouti locus genotype.-Four of nine hepatic enzyme activities assayed simultaneously differed between eight-week-old yellow (A(y)/-, A(vy)/-) and non-yellow (A/-, a/a) male inbred and F(1) hybrid mice. Among these four, only cytoplasmic malic enzyme activity was elevated in all yellow mice, as compared with the non-yellow sibs, regardless of background genome. Glucokinase, serine dehydratase, and tyrosine alpha-ketoglutarate transaminase activities were also changed in yellow mice, but these alterations depended on the background genome.-The ratio of malic enzyme activity to citrate-cleavage enzyme activity, possibly related to the altered fat metabolism of yellow mice, was influenced by background genome as well as by the yellow genotype.--Significant deviations of enzyme activities from mid-parent values among F(1) hybrids were associated with particular background genomes; the number of such deviations was larger among yellow mice than among non-yellows and this difference was greater among C3H F(1) hybrids than among C57BL/6 F(1) hybrids.
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PMID:Influence of background genome on enzymatic characteristics of yellow (A v -, A vy -) mice. 440 52


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