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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of advanced cervical carcinoma of the uterus with ectopic adrenocorticotrophic hormone (ACTH) syndrome is described. The patient was seen for general malaise 21 months after surgical treatment of the primary lesion whose histology was undifferentiated small cell carcinoma of the uterine cervix. She had extensive metastases in the liver and the abdominal wall. In addition to the typical clinical manifestations of Cushing's syndrome such as moon face, central obesity and acne vulgaris, hyperglycemia was so severe that she was in a hyperosmolar non-ketotic coma. Endocrinological examinations revealed elevated plasma ACTH and cortisol, and urinary excretion of 17-hydroxycorticosteroids and 17-ketosteroids, which were not suppressed by high-dose dexamethasone administration. Based on these clinical and laboratory findings, a diagnosis of ectopic ACTH syndrome was made. Among the results of other endocrinological examinations conducted to find the etiological cause of the hyperglycemic coma, which seemed to be unusual for ectopic ACTH syndrome, the plasma somatostatin level was abnormally high. Metastatic tumors in the liver obtained at the time of autopsy contained large amounts of both ACTH and somatostatin, and gel filtration studies revealed that the peptides produced by the tumor had the molecular sizes of the biologically active forms of the respective peptides. These observations suggest possible involvement of the somatostatin in deteriorating glucose intolerance to develop hyperglycemic hyperosmolar non-ketotic coma as a drastic disturbance of metabolism.
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PMID:A case of cervical carcinoma of the uterus presenting with hyperosmolar non-ketotic coma as a manifestation of ectopic adrenocorticotropic hormone syndrome. 164 12

The present study was designed to determine whether the diminution of growth hormone (GH) secretion that occurs in obese Zucker rats is related to alterations of GH-releasing factor (GRF) or somatostatin (SRIF) pituitary binding sites. Cold saturation studies were performed in pituitary homogenates of 4-month-old lean and obese rats, using [125I-Tyr10]hGRF(1-44)NH2 as radioligand and [127I-Tyr10]hGRF-(1-44)NH2 as competitor, and in pituitary membrane preparations, using [125I-Tyr0, D-Trp8]SRIF14 as radioligand and [127I-Tyr0, D-Trp8]SRIF14 as competitor. In lean rats, analysis of the curves by the Ligand program revealed the presence of two distinct classes of GRF binding sites, the first being of high affinity (0.74 +/- 0.11 nM) and low capacity (118 +/- 31 fmol/mg protein), the second being of lower affinity (880 +/- 240 nM) and higher capacity (140 +/- 35 pmol/mg protein), and of a single class of SRIF binding sites (affinity: 0.40 +/- 0.12 nM; capacity: 24 +/- 6 fmol/mg protein). In obese rats, no difference was observed in GRF binding parameters for both classes of sites, but the concentration of somatostatin binding sites was reduced by 67% when compared to their lean littermates. These findings suggest that the SRIF pituitary receptors are down-regulated in obese Zucker rats and indicate that no alteration of GRF pituitary binding sites contribute to the blunted GH secretion observed in this model of obesity.
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PMID:Alteration of somatostatin but not growth hormone-releasing factor pituitary binding sites in obese Zucker rats. 168 74

Central and lateral hypothalamic concentrations of 9 regulatory peptides implicated in the control of feeding behaviour were measured in corpulent (cp/cp) JCR:LA-cp rats which develop spontaneous obesity, hyperinsulinaemia and hyperlipidaemia, and in lean (+/?) controls. In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls. Following food restriction with a 16% reduction in body weight, these differences were apparently reversed and there were also significant rises in the lateral hypothalamic concentrations of neurotensin and of galanin. The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted. Male cp/cp rats showed no significant differences from lean males in central or lateral hypothalamic concentrations of any of the 9 peptides. NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally. Disturbances in these putative appetite-regulating peptides may be involved in the hyperphagia and other hypothalamic abnormalities in this spontaneous obesity syndrome. The apparent absence of differences between the male corpulent and lean groups may relate to sexual dimorphism of the syndrome, which is more marked in the females.
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PMID:Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat. 172 Mar 64

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.
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PMID:Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. 194 36

It is known that obese subjects have a blunted GH secretory response to stimulation, but little is known about the inhibition of GH secretion in obesity. The present study was designed to evaluate the effects of obesity on the suppression of GH by hyperglycemia and/or somatostatin. Plasma GH concentrations were measured in eight nondiabetic obese subjects and eight nonobese healthy controls during a 4-h hyperglycemic clamp. During the third hour synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min. Baseline plasma GH levels were similar in obese and nonobese subjects (0.9 +/- 0.1 vs. 0.8 +/- 0.2 micrograms/L; mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma GH averaged 0.8 +/- 0.1 micrograms/L in obese patients and 0.4 +/- 0.1 micrograms/L in control subjects (P less than 0.01), with a reduction of 6 +/- 5% in the former and 35 +/- 10% in the latter (P less than 0.01). In both groups somatostatin infusion did not result in a further decrease in plasma GH. Discontinuation of the somatostatin infusion resulted in a rise in both groups; the increase was higher in nonobese subjects (8.1 +/- 3.8 vs. 2.3 +/- 0.9 micrograms/L in the period 220-240 min; P = NS). These results suggest that in human obesity, hyperglycemia has a diminished inhibitory effect on GH secretion, and somatostatin administration has no additional effect in either obese or nonobese nondiabetic subjects.
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PMID:Plasma concentrations of growth hormone during hyperglycemic clamp with or without somatostatin infusion in obese subjects. 197 27

The response of circulating somatostatin-like immunoactivity (SLI) to oral glucose and its relation to other pancreatic islet cell hormones were studied in 10 hypothyroid subjects before and after treatment. None of the patients suffered from diabetes mellitus or obesity. Compared with normal controls, the hypothyroid subjects had higher fasting and stimulated SLI levels but lower fasting pancreatic glucagon levels. Integrated glucose and insulin responses following glucose ingestion were normal, but the peak insulin response was delayed to 120 min suggesting impaired pancreatic beta-cell response to oral glucose. On the other hand, the peak response of plasma C-peptide was higher probably because of a reduction in metabolic clearance. In both hypothyroid subjects and controls, a significant correlation was found between the maximal increment of SLI and the maximal decrement of glucagon following oral glucose. In conclusion, plasma SLI is increased in hypothyroidism. The changes in SLI may be due to either an increased hormonal secretion or a reduced metabolic clearance in hypothyroidism. This elevated SLI might contribute to the slower gastrointestinal motility observed in hypothyroidism. Our data also suggest that the reduction in glucagon secretion may be secondary to the increase in circulating SLI.
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PMID:Circulating somatostatin after oral glucose in hypothyroidism. 197 68

In the present study we evaluated the regulation of plasma free fatty acid (FFA) concentration by glucose and insulin in human obesity. To this purpose we measured plasma FFA concentration in normoglycemic, normoinsulinemic obese (n = 8) and nonobese (n = 8) healthy subjects during 240 min of exogenous hyperglycemia (hyperglycemic glucose clamp) in presence of both glucose-stimulated (0-120 min and 180-240 min) and somatostatin-inhibited (120-180 min) insulin secretion. We found that plasma FFA curves were roughly parallel in the 0-120 min period and FFA values of obese subjects were constantly higher throughout the experimental period. Moreover, the difference between the two groups was significant when individual data were expressed as a percent of fasting FFA value (P less than 0.0001 from 0 to 120 min). Plasma insulin levels were similar in the two groups during the entire study. The amount of glucose metabolized during the 80-120 min period was significantly lower in obese than in nonobese subjects (172 +/- 7 v. 341 +/- 11 mg/m2.min, P less than 0.01; means +/- s.e.). During the somatostatin period (120-180 min) plasma insulin was lowered close to basal values in both groups (116 +/- 15 and 109 +/- 11 pmol/l) and plasma FFA concentrations rose in a linear fashion. Our data suggest that suppression of plasma FFA concentrations by glucose and insulin is qualitatively similar in healthy nonobese and obese subjects, the latter having higher FFA values. Insulin action on FFA metabolism isn ot grossly impaired in obese subjects who are clearly insulin resistant as far as glucose metabolism is concerned.
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PMID:Plasma free fatty acid concentration during hyperglycemic glucose clamp with and without somatostatin infusion in obese subjects with normal glucose tolerance. 197 21

GH secretion is markedly blunted in obesity; however, the mechanism(s) mediating this response remains to be elucidated. In the present study we examined the involvement of the two hypothalamic GH-regulatory hormones, GH-releasing factor (GRF) and somatostatin (SRIF), using the genetically obese male Zucker rat. Spontaneous GH, insulin, and glucose secretory profiles obtained from free moving, chronically cannulated rats revealed a marked suppression in amplitude and duration of GH pulses in obese Zucker rats compared to their lean littermates (mean 6-h plasma GH level, 3.9 +/- 0.4 vs. 21.5 +/- 3.8 ng/ml; P less than 0.001). Obese rats also exhibited significant hyperinsulinemia in the presence of normoglycemia. The plasma GH response to an iv bolus of 1 microgram rat GRF-(1-29)NH2, administered during peak and trough periods of the GH rhythm, was significantly attenuated in obese rats at peak (137.4 +/- 26.1 vs. 266.9 +/- 40.7 ng/ml; P less than 0.02), although not at trough, times. Passive immunization of obese rats with a specific antiserum to SRIF failed to restore the amplitude of GH pulses to normal values; the mean 6-h plasma GH level of obese rats given SRIF antiserum was not significantly different from that of obese rats administered normal sheep serum. Both pituitary wet weight and pituitary GH content and concentration were reduced in the obese group. Measurement of hypothalamic GRF immunoreactivity revealed a significant (P less than 0.05) reduction in the mediobasal hypothalamic GRF content in obese rats (503.2 +/- 60.1 pg/fragment) compared to that in lean controls (678.1 +/- 50.2 pg/fragment), although no significant difference was observed in hypothalamic SRIF concentration. Peripheral SRIF immunoreactive levels were significantly (P less than 0.01) elevated in both the pancreas and stomach of obese rats. These results demonstrate that the genetically obese Zucker rat exhibits 1) marked impairment in both spontaneous and GRF-induced GH release, which cannot be reversed by SRIF immunoneutralization, 2) significant reduction in pituitary GH concentration, 3) depressed hypothalamic GRF content, and 4) elevated gastric and pancreatic, but not hypothalamic, SRIF levels. The findings suggest that the defect in pituitary GH secretion observed in the genetically obese Zucker rat is due, at least partially, to insufficient stimulation by hypothalamic GRF, and that SRIF does not play a significant role.
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PMID:Mechanisms of impaired growth hormone secretion in genetically obese Zucker rats: roles of growth hormone-releasing factor and somatostatin. 197 30

The aim of the present study was to evaluate whether the inhibitory effect on pancreatic A-cell exerted by hyperglycemic hyperinsulinemia and/or by somatostatin administration is impaired in human obesity. For this purpose plasma glucagon concentrations were measured in 8 obese and 8 nonobese nondiabetic subjects during a 4-h hyperglycemic clamp. Synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min during the third hour of the study. Fasting plasma glucagon was higher in obese than in nonobese subjects (242 +/- 32 vs 163 +/- 15 pg/ml, p less than 0.05) (mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma glucagon averaged 195 +/- 26 pg/ml in obese and 122 +/- 13 pg/ml in nonobese subjects (p less than 0.05), with a reduction of 19 +/- 3% in the former and 28 +/- 4% in the latter (p = n.s.). In both groups somatostatin infusion did not result in a further decrease in plasma glucagon, which averaged 192 +/- 27 pg/ml in obese and 123 +/- 16 pg/ml in nonobese subjects (p less than 0.05) in the 160-180 min period of the study. Also after discontinuing somatostatin infusion plasma glucagon levels did not change. These results suggest that in human obesity hyperglycemic hyperinsulinemia has a normal inhibitory effect on pancreatic A-cell and that somatostatin administration has no additive effect on hyperglycemia and hyperinsulinemia in either obese or nonobese nondiabetic subjects.
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PMID:Plasma concentrations of glucagon during hyperglycemic clamp with or without somatostatin infusion in obese subjects. 198 86

Administration of monosodium glutamate (MSG) to neonatal rodents produces permanent lesions of hypothalamic arcuate neurons that secrete GH-releasing hormone (GHRH). The present study was intended to determine the consequences of GHRH deficiency on the pulsatile GH secretory pattern and growth in MSG-treated female rats and to compare these effects with those observed in male littermates. Male and female rats were injected with MSG [4 mg/g body wt (BW), sc] or saline (controls) on days 2, 4, 6, 8, and 10 after birth. Immunoreactive GHRH concentrations were decreased in the hypothalamus (by 60%) and in the median eminence (by 95%) of adult male and female MSG-treated rats. In contrast, somatostatin concentrations were unaffected. BW and linear growth were severely impaired in male MSG-treated rats, but in MSG-lesioned females BW was not different from controls, and the attenuation of longitudinal growth was less severe and the obesity more pronounced than in males. These sex differences occurred despite similar reductions (by 55%) in serum insulin-like growth factor I concentrations in male and female MSG-treated rats. MSG treatment also produced decreases in pituitary wt and GH content (by 60%), independent of sex. Pulsatile GH secretion was studied by serial blood sampling of chronically cannulated, freely moving rats. Plasma GH patterns were analyzed by the PULSAR program. Compared to controls, treatment with MSG led to a marked inhibition (by 90%) of GH secretion in both sexes. Significant reductions in GH pulse amplitude (-95%) and pulse duration (-62%) were observed in males, whereas pulse amplitude (-85%), pulse frequency (-67%), and baseline GH concentrations (-80%) were markedly reduced in females. The GH responses to an iv bolus injection of rat GHRH (1 microgram/rat) was severely blunted in both male and female MSG-treated rats. This study demonstrates that GHRH deficiency in female rats results in a marked inhibition of GH pulses, as in males, but also causes severe and sex-specific reductions in GH basal secretion and pulse frequency. These observations suggest that hypothalamic GHRH secretion in female rats is more continuous than in males and is a determinant of the elevated interpulse secretion of GH. Moreover, body wt and linear growth are less severely affected by arcuate lesions in female animals, compared to males. These sex-related differences in growth rates may result in part from the tendency of female MSG-lesioned rats to become more obese than males, and the development of obesity, in turn, may antagonize the factors that tend to slow linear growth.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neonatal treatment with monosodium glutamate: effects of prolonged growth hormone (GH)-releasing hormone deficiency on pulsatile GH secretion and growth in female rats. 198 48


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