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

To clarify the possible neuroendocrine mechanisms underlying the impairment in growth hormone (GH) secretion present in obesity, the GH response to GH-releasing hormone (GHRH, N = 6), insulin hypoglycemia (N = 6), clonidine (N = 7) and arginine (N = 8) after GHRH pretreatment (1 microgram/kg iv 2 h before the tests) was evaluated in 27 obese peripubertal children and in a group of normal-weight short-normal children (N = 26). Growth hormone-releasing hormone pretreatment and all further stimuli elicited a statistically significant GH response in both obese and short-normal children; in the latter group arginine did not induce a significant GH response. No differences were found among the GH responses after the second stimuli in obese children, while in short-normal children the arginine peak and area values were lower than after GHRH and clonidine. Comparison between the two groups showed similar baseline but higher stimulated GH levels in normal-weight children after all tests except arginine, after which no difference was present. In conclusion, the neuroregulation of GH release seems to be similar qualitatively in normal-weight and obese youngsters; the different behavior observed after arginine, which is supposed to act through somatostatin inhibition, might be due to a chronic increase in somatostatinergic tone responsible for the lower stimulated GH levels in obesity.
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PMID:Growth hormone response to growth hormone-releasing hormone (GHRH), insulin, clonidine and arginine after GHRH pretreatment in obese children: evidence of somatostatin increase? 778 12

Amylin (islet-associated polypeptide) is a 37-amino acid peptide that is cosecreted with insulin from the pancreatic beta-cell. Accurate measurement of its plasma levels is important for delineating the physiological range over which amylin acts. We describe a reproducible, highly specific, and sensitive radioimmunoassay for direct measurement of plasma amylin-(1-37). We measured changes in portal and systemic plasma amylin and insulin in three groups of anesthetized rats: lean young adult and old adult Wistar rats with acquired obesity, and Wistar fatty [WDF/TaFa (fa/fa)] rats, a model of genetic obesity and insulin resistance derived from the Wistar strain. Changes in response to fasting, feeding, and intravenous stimulation with glucose plus arginine were assessed. We find that the amylin-to-insulin ratio is constant in fasted or fed young and old rats because of proportionate increases in both entities with aging. In genetically obese Wistar rats, amylin and insulin levels are three- to tenfold higher than in lean young or obese old normal controls. Islet stimulation by feeding or intravenous glucose plus arginine resulted in a decreased amylin-to-insulin molar ratio in all groups. When normalized for the degree of islet stimulation, amylin-to-insulin ratios were significantly elevated in genetically obese vs. normal rats, both in the portal and systemic circulation. These results demonstrate that aging-related weight gain in normal rats is associated with moderate and proportional increases in amylin and insulin, whereas genetic obesity is characterized by elevated amylin and an increased amylin-to-insulin ratio. Implications for the pathogenesis of insulin resistance and obesity are discussed.
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PMID:Direct plasma radioimmunoassay for rat amylin-(1-37): concentrations with acquired and genetic obesity. 804 5

We have studied the responses of insulin and somatostatin to glucose and arginine in the perfused pancreas of GK rats, which spontaneously develop mild noninsulin-dependent diabetes without concomitant obesity. Our GK rats have been obtained after at least 42 generations of inbreeding of Wistar rats with initial selection for increased blood glucose levels during glucose tolerance tests. During perfusion with a high (16.7 mmol l-1) glucose concentration, normal responses of insulin and somatostatin were found in pancreata from non-diabetic control rats. In GK pancreata, however, these responses were virtually abolished. When the glucose concentration of the perfusion medium was switched from 16.7 to 3.3 mmol l-1 glucose, a transient increase- 'off-response' -in both insulin and somatostatin secretion was noted in GK but not in control pancreata. During the subsequent stimulation with arginine (20 mmol l-1), insulin and somatostatin responses were similar in pancreata from non-diabetic and GK rats. The pancreatic content of insulin did not differ between non-diabetic and GK rats, whereas the content of somatostatin was increased by 56% (P < 0.025) in GK glands. In conclusion, abnormalities assigned to pancreatic hormone secretion in the GK rat comprise not only markedly impaired insulin but also somatostatin response to glucose. Since there was no decrease in pancreatic content of these hormones in GK rats, the cause of glucose insensitivity of the hormone-producing cells is likely to reside in a defective stimulus-secretion coupling rather than decreased availability of the hormones.
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PMID:Both somatostatin and insulin responses to glucose are impaired in the perfused pancreas of the spontaneously noninsulin-dependent diabetic GK (Goto-Kakizaki) rats. 810 4

Enterostatin is a peptide which has been found to decrease food intake with a specificity for the fat contained in the food. In this work we have investigated the effect of enterostatin (Val-Pro-Asp-Pro-Arg) and its proteolytic fragments, des-arg-enterostatin (Val-Pro-Asp-Pro) and the tripeptide Asp-Pro-Arg, on insulin secretion. It was found that enterostatin and desarg-enterostatin inhibited insulin secretion from isolated rat islets by 55.3% (P < 0.05) and 53.6% (P < 0.05) at 1.6 x 10(-4) M concentration, while the tripeptide Asp-Pro-Arg at 1.6 x 10(-4) M concentration had no significant effect and increased insulin secretion by 33.0%. Enterostatin at 200 ng after intraventricular administration was found to inhibit the intake of a high-fat diet by 45.0%, while des-arg-enterostatin (200 ng) had no effect, in agreement with previous findings. The tripeptide Asp-Pro-Arg (200 ng) had no effect on the intake of a high-fat diet compared to saline injection. The ability of enterostatin to inhibit high-fat food intake and decrease insulin secretion may be important for the prevention of obesity and type II diabetes, conditions linked through hyperinsulinemia.
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PMID:Enterostatin--its ability to inhibit insulin secretion and to decrease high-fat food intake. 811 74

Obesity is one of the factors which limits the value of growth hormone (GH) provocation tests in the diagnosis of GH deficiency. We have therefore examined (1) the relationship between urinary GH (uGH), a physiological parameter of GH secretion, and percent ideal body mass index (BMI%), an indirect estimate of body fat, in 528 schoolchildren; and (2) the extent to which peak arginine stimulated (0.5 g/kg i.v.) GH concentrations were influenced by BMI% in 176 short normal (SN) children and 48 girls with Turner syndrome (TS). The mean BMI% (SD) for each group was 102.9 (10.8) in schoolboys, 102.7 (13.4) in schoolgirls, 95.8 (13.9) in SN boys, 98.2 (21.4) in SN girls and 105.9 (18.0) in TS. BMI% correlated inversely with log uGH in school-children (boys r = -0.16, P = 0.01; girls r = -0.25, P < 0.001). However, if each sex was subdivided by pubertal status, the inverse relationship only persisted in pubertal (boys r = -0.18, P = 0.04; girls r = -0.39, P < 0.001) but not prepubertal children (boys r = -0.1, P = 0.3; girls r = -0.11, P = 0.3). BMI% was also inversely related to log peak stimulated GH concentration in SN girls (r = -0.49, P < 0.001) but not SN boys (r = -0.14, P = 0.2) or girls with TS (r = 0.19, P = 0.2). The inverse relationship between normal body fat and physiological GH secretion becomes significant during puberty; in girls it accounts for 15% of the variability in uGH excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of body mass index on growth hormone secretion in normal and short statured children. 819 82

Using the molecular scanning technique of single-stranded conformational polymorphism (SSCP), we have examined the exons encoding the insulin receptor gene in 26 patients with syndromes of insulin resistance. We found 27 variant sequences, 4 of which were mutations that altered an amino acid. One patient with the Rabson-Mendenhall syndrome was homozygous for a mutation in the extracellular alpha-subunit (Ser to Leu323), one type A insulin-resistant patient was heterozygous for Pro to Leu1178, and another type A insulin-resistant patient was heterozygous for a mutation in the COOH-terminus of the receptor (Arg to Gln1351). The previously reported, and probably functionally insignificant, variant Val to Met985 was detected in one patient. No missense or nonsense insulin receptor mutations were found in any patients whose insulin resistance was associated with gross obesity, lipoatrophy, or acromegaloid features. No missense or nonsense mutations were found in subjects with polycystic ovary syndrome or Syndrome X. Putting these findings in the context of other work in this field, we conclude that subjects with leprechaunism or Rabson-Mendenhall syndrome have a high probability of having a missense or nonsense insulin receptor mutation. Nonobese, nondysmorphic, severely insulin-resistant females with hirsutism, acanthosis nigricans, and menstrual disturbance (type A phenotype) have an intermediate probability of having this type of insulin receptor mutation. Although insulin receptor mutations have been occasionally described in other phenotypes of insulin resistance, the frequency of point mutations in the exons of the insulin receptor gene in patients with those phenotypes appears to be low.
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PMID:Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. 831 8

To test the hypothesis that the high circulating FFA levels in the diabetes of obesity could contribute to the altered dynamics of insulin secretion seen in that condition, insulin release was measured in isolated perifused rat islet cells, without or with added palmitate. Acutely, as in other systems, palmitate (1 mM) stimulated insulin release. Palmitate (1 mM) suppressed both first and second phase insulin release after 2, 3, or 4 h of perifusion, but not after 1 h. No significant effect was noted with 0.3 mM palmitate, and the effect was maximal at 1 mM. The stimulatory effects of arginine were essentially unaffected. Tolbutamide (1 mM) reversed or counteracted the effect. Glucose oxidation was suppressed in islets incubated with 1 mM palmitate for 4 h. Inhibitors of fat oxidation, alpha-bromostearate (1 mM) and methyl-3-tetradecylglycidate (100 microM) reversed the effects of palmitate on glucose-stimulated insulin release and glucose oxidation. Thus, prolonged incubation of rat islet cells with 1 mM palmitate could suppress the glucose-stimulated release of insulin from perifused rat islets. This suppression could be reversed by inhibitors of fat oxidation. This supports the hypothesis that elevated FFA levels and/or increased fat oxidation could contribute to the altered dynamics of insulin secretion in obese diabetics by fuel antagonism as well as the previously documented suppression of peripheral glucose uptake and stimulation of hepatic gluconeogenesis and may be a key link between obesity and the development of diabetes.
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PMID:Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release. 831 69

Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p < 0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p < 0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity.
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PMID:Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity? 834 45

The prevalence of obesity is increasing in the developed as well as underdeveloped countries. Obesity in women is associated with reproductive disorders. The levels of estrone and androgens are higher in obese women along with a reduction in the levels of sex hormone binding globulin ( SHBG ). The pituitary secretion of hormones is altered either due to a deficient peripheral feedback regulation or a concomitant central defect in the obese. Luteinizing hormone ( LH ) level may increase in some of the obese subjects. The secretion of LH in response to luteinizing hormone releasing hormone ( LHRH or GnRH ), clonidine and naloxone may be altered in obese women. The levels of circulating prolactin may fall along with a delay in the nocturnal surge of the hormone. The secretion of prolactin in response to thyrotropin releasing hormone ( TRH ), insulin-induced hypoglycemia, arginine and chlorpromazine is altered. Similarly growth hormone secretion in response to growth hormone releasing hormone ( GHRH ), clonidine, naloxone and arginine is also altered in obesity. The literature suggests an alteration in the autonomic nervous system activity and the metabolism of carbohydrates and fats in the obese. Steroid hormones could affect the distribution of fat in the various regions of the body, and the distribution of body fat is linked with the severity of hyperandrogenism and metabolic disorders in obese subjects. However, it is heartening to note that many of the endocrinological and reproductive disorders are reversible with weight reduction in the obese subjects.
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PMID:Reproductive functions in obese women. 837 28

To examine the cause of hyperinsulinemia in obesity, we determined plasma glucose, insulin, and C peptide responses to glucose (75g), arginine (0.5 g/kg body weight), and glucagon (1mg) in seven normal subjects and 20 obese subjects before and after weight loss by very low calorie diet therapy (Optifast, 240 kcal/day for 8 to 12 weeks). Integrated insulin and C peptide secretion in response to three different stimuli were markedly increased before weight loss and were significantly decreased following weight loss in response to glucose (mean +/- s.e. 36.6 +/- 6.4 vs. 18.4 +/- 2.6; 148.2 +/- 12.0 vs. 113.1 +/- 8.7 pmol/ml/h; P < 0.01), arginine (13.8 +/- 2.2 vs. 8.2 +/- 2.1; 94.8 +/- 11.2 vs. 66.0 +/- 6.1 pmol/ml/h; P < 0.01), and glucagon (16.5 +/- 2.7 vs. 10.7 +/- 1.5; 89.0 +/- 6.0 vs. 68.7 +/- 4.8 pmol/m/h; P < 0.01). The molar ratio of integrated C peptide to integrated insulin in response to all three stimuli was markedly decreased before, and this ratio significantly increased following weight loss (mean +/- s.e., 5.01 +/- 0.41 vs. 7.45 +/- 0.65; P < 0.01), and to arginine (7.78 +/- 0.61 vs. 10.97 +/- 1.28; P < 0.05), but not to glucagon (6.72 +/- 0.60 vs. 7.47 +/- 0.66). These findings suggest that both increased insulin secretion and decreased insulin clearance contribute to hyperinsulinemia in obese subjects. Improvement in these abnormalities to all three stimuli after weight loss also suggests that hyperinsulinemia in obesity is a consequence of the obesity itself rather than a pre-existing disorder.
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PMID:Very low calorie diet-induced weight loss reverses exaggerated insulin secretion in response to glucose, arginine and glucagon in obesity. 838 64


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