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

To analyze B-cell mechanisms in obesity, we measured the relationship (slope of potentiation) between glucose levels and acute insulin responses (AIR) to isoproterenol or arginine in nondiabetic subjects ranging from lean to markedly obese. Obese men (n = 9) had higher AIRs to isoproterenol than lean men (n = 11) at basal glucose levels [52 +/- 9 (SEM) vs. 32 +/- 5 microU/mL; P less than 0.05], and the difference increased as the ambient glucose level was raised (at 230 mg/dL; 263 +/- 22 vs. 140 +/- 21 microU/mL; P less than 0.0008). The individuals' slopes of glucose potentiation of AIR to isoproterenol were positively correlated with their excess weight (r = 0.72; P less than 0.001). Similar results were found when arginine was used as the secretagogue in other men and in women; the slope of potentiation was positively correlated with excess weight in both men and women (both P less than 0.005), although the effect of excess weight on slope was 51% greater among men (P less than 0.03). An independent measurement of insulin sensitivity (the Bergman SI) was made in the women. The potentiation slope was inversely correlated with SI (P less than 0.0001), indicating that the effect of obesity on insulin secretion is correlated with insulin resistance. These results characterize one mechanism contributing to the hyperinsulinemia of obesity and highlight the importance of considering the prevailing insulin sensitivity when assessing islet function.
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PMID:Relationship of islet function to insulin action in human obesity. 329 80

Obese subjects show a subnormal growth hormone (GH) and prolactin (PRL) release in response to a variety of stimuli. Fenfluramine, an anorexiant drug used in obesity therapy, may have some effects on hypothalamic-pituitary function mediated by serotoninergic stimulation. The present investigation in obese subjects was carried out to study the effects of fenfluramine (60 mg orally) on GH and PRL secretion after intravenous arginine infusion. Ten volunteer obese females were studied and compared with 10 volunteer normal weight controls. In the obese group the GH response to arginine was significantly lower than in control group. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. The PRL response to arginine in obese women was subnormal. Fenfluramine administration restored the response of PRL to arginine infusion to normal. In conclusion, fenfluramine--under acute circumstances--enhances the hypothalamic-pituitary response to arginine in obese subjects. The decreased GH and PRL output in obese subjects is not due to an absolute hormonal deficiency and this effect of fenfluramine on GH secretion may--due to its lipolysis stimulation--be useful in obesity treatment.
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PMID:Effect of fenfluramine on growth hormone and prolactin secretion in obese subjects. 343 16

It is demonstrated that pre-obese Zucker rats, studied before weaning (17 days of age), at a time when they were indistinguishable from lean controls, do hypersecrete insulin in response to glucose or arginine administration when compared to their lean littermates in spite of normal basal insulin levels. When arginine is used as the stimulus, it is shown that pre-obese pups hypersecrete glucagon as well as insulin, the net result of insulin and glucagon oversecretion being probably the observed normoglycemia of these animals. Furthermore, these early substrate-induced increases in pancreatic hormonal secretion could be reduced toward normal values by acute pre-treatment of the pre-obese rats with the cholinergic inhibitor, atropine. It is suggested the parasympathetic nervous system plays a role in genetically obese fa/fa rats in bringing about an early increased substrate-induced insulin release, a defect which could be one of the causes involved in the development of their obesity syndrome. In adult animals, the involvement of the parasympathetic nervous system in insulin oversecretion is less clear probably due to the presence of an increased B cell mass. However, using three different experimental approaches, it could be seen that an increased vagal tone acting at the B cells in obese animals participate to their insulin hypersecretion.
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PMID:A role for the vagus nerve in the etiology and maintenance of the hyperinsulinemia of genetically obese fa/fa rats. 390 50

A comparison of the somatostatin with the insulin and glucagon secretions in hypothalamic obesity and genetic obesity was made using the isolated perfused pancreas of rats. In our perfusion experiment, the somatostatin response to 19 mM arginine in the presence of 4.4 mM glucose was significantly greater in both ventromedial hypothalamus (VMH)-lesioned and Zucker fa/fa rats than in their controls, as was the perfusate insulin. The perfusate arginine-stimulated glucagon secretion appeared no different in obese and control rats. Because hyperinsulinemia in vivo and hyperresponses to arginine of perfusate insulin and somatostatin were observed in both VMH-lesioned and Zucker fa/fa rats, whereas the perfusate glucagon secretion in the presence of 4.4 mM glucose was unchanged by obesity, the secretory behavior of some pancreatic hormones seems similar in VMH-lesioned and Zucker fa/fa rats in certain conditions. These results suggest that some abnormalities of pancreatic hormone secretion may be caused by a mechanism common to obesity, whether caused experimentally or genetically.
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PMID:Somatostatin, insulin, and glucagon secretion from isolated perfused pancreas of obese rats. 611 83

Changes in insulin, somatostatin, and glucagon secretion during the development of obesity in rats after ventromedial hypothalamic (VMH) lesions were evaluated by measuring fasting hormone levels and their secretion from the isolated perfused pancreas. Fasting peripheral insulin levels were not altered 1 week after the VMH lesions but became progressively elevated at 3-4, 8-9, and 11-12 weeks compared to the values in sham-operated and age-matched control rats. In the portal vein, insulin levels also progressively increased in VMH-lesioned rats, but the portal-peripheral gradient of insulin in the later phase of VMH obesity was significantly lower than in the early phase after VMH lesions. On the contrary, the arginine-induced insulin release from the perfused pancreas was highest at 1 week and gradually decreased thereafter, although it continued to remain higher than that of controls. The perfusate somatostatin response to arginine also was exaggerated in the VMH-lesioned rats. However, both the peripheral glucagon level and the glucagon secretion from the perfused pancreas of the VMH-lesioned rats were not significantly different from the controls. These results show that VMH lesions result in an increased insulin and somatostatin secretion. Using the cyclically perfused liver in situ, we have found that the hepatic extraction rate of insulin is indeed reduced in rats 8-9 weeks after VMH lesioning, and so have at least partly accounted for the decreased portal-peripheral gradient of insulin in the later VMH postoperative phase.
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PMID:Changes in insulin, somatostatin, and glucagon secretion during the development of obesity in ventromedial hypothalamic-lesioned rats. 614 Jan 60

Diabetes mellitus in the adult Chinese hamster is characterized by subnormal pancreatic insulin release in vitro, decreased insulin content, and lack of obesity. The cause of the islet B-cell failure is not clear. We measured insulin, glucagon, and somatostatin release from in vitro perfused pancreases of young (mean age 10 and 20 weeks), genetically diabetic animals (subline AC, mean plasma glucose 8.0 and 16.6 mmol/l, respectively). Compared to age- and sex-matched normal hamsters (subline M, mean plasma glucose 5.3 mmol/l), the younger diabetic animals had a significantly elevated mean plasma glucose level, but net in vitro pancreatic release of insulin, glucagon, and somatostatin was normal. Pancreatic content of insulin and glucagon was also not significantly different from normal. At age 20 weeks, when the plasma glucose of the diabetic animals was even more elevated, pancreatic content and release of insulin were significantly subnormal, whereas glucagon and somatostatin release were normal, and pancreatic content of glucagon was normal. In a similar group of young (mean age 10 weeks) diabetic animals, non-fasting plasma insulin levels were within the normal range, but the corresponding glucose levels were excessive in most of the animals (13 out of 19). In conclusion, 10-week-old diabetic hamsters show mild hyperglycaemia which cannot be accounted for directly by decreased pancreatic release in response to a glucose plus arginine stimulus in vitro. Decreased ability of the B cell to respond in vivo to hyperglycaemia or peripheral resistance to insulin may contribute to later B-cell failure in the older diabetic hamster.
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PMID:Insulin, glucagon, and somatostatin release from the prediabetic Chinese hamster. 614 71

Forty patients with the Prader-Willi syndrome have been examined. The typical features begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later. The average height of the patients in this series who were admitted to the Clinical Study Center was 149 cm and their weight was 114 kg. The weight and height curves show that Prader-Willi individuals are consistently shorter and heavier than normal children. Tests of endocrine function showed normal glucose tolerance. Insulin secretion was increased in relation to obesity. The rise in growth hormone (hGH) after injecting insulin to induce hypoglycemia and after the infusion of arginine was comparable to other obese individuals but was low in comparison to normal weight subjects. There was no rise in growth hormone with L-dopa administration, but there was a rise in hGH with the administration of 2-deoxy-D-glucose. The hypoglycemia produced by insulin was greater in the Prader-Willi patient than in obese controls. The rise in TRH (thyrotropin-releasing hormone) following the injection of TSH (thyrotropin stimulating hormone) was greater in the Prader-Willi patients than in the obese controls. Hypogonadism was routine in this series, and the response to LRH (luteinizing releasing hormone) was absent in all tested subjects. Treatment with clomiphene for 30 to 90 days significantly increased the response to LRH in three adult individuals who had not been treated with gonadal steroids previously and who were hypogonadal. Rectal temperature declined in three of the five Prader-Willi patients during exposure to an ambient temperature of 4 degrees C, but none of the three obese controls showed a decline. Food intake averaged 5167 kcal/d when six patients were given trays containing more food than they could eat. Food intake was not reduced when tryptophan was added to the diet. Salivary secretion was reduced in the Prader-Willi patients. A number of pulmonary function tests were significantly reduced in the study patients compared to obese or normal weight controls. The anatomic findings in four autopsied patients with the Prader-Willi syndrome showed no significant differences from those of obese subjects without this syndrome. The chromosomal pattern showed a deletion or translocation at chromosome 15 in 3 of 12 patients in whom this test was performed. These findings in 40 patients with the Prader-Willi syndrome have been compared with the information contained in 159 reports published in the medical literature.
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PMID:The Prader-Willi syndrome: a study of 40 patients and a review of the literature. 633 43

We studied insulin-like growth factors (IGF) I and II, prolactin, and the insulin response to arginine in 19 children with craniopharyngioma and documented growth hormone deficiency. Patients were divided into three groups according to their growth rate during the first postoperative year. Seven patients with excessive growth (Group A) had hyperinsulinism, normal IGF values, elevated basal prolactin levels, and a delayed thyrotropin response to thyrotropin-releasing hormone, which was compatible with hypothalamic lesions. In the six patients with normal growth (Group B), the insulin level was low; all other hormone values were similar to those of Group A. In the six patients with decreased growth (Group C), levels of IGF I, insulin, prolactin, and thyrotropin were low, indicating the presence of severe pituitary damage and explaining the failure to grow. Patients in all groups had low or undetectable basal levels of growth hormone. We conclude that in Group B, normal IGF permitted normal growth, and prolactin hypersecretion may have been responsible for normal IGF I values. Excessive growth in Group A may have been caused by hyperinsulinism associated with hyperphagia and obesity of hypothalamic origin.
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PMID:Insulin-like growth factors I and II, prolactin, and insulin in 19 growth hormone-deficient children with excessive, normal, or decreased longitudinal growth after operation for craniopharyngioma. 635 37

12 patients (9 male, 3 female) with the Prader-Labhart-Willi-Syndrome (PLWS) were examined, and had medical treatment. Small stature varied in degree; body-height was found below the 25th percentile of normal height in 9 of the patients, 6 of them ranged along or below the 3rd percentile. Growth-hormone (GH) was measured after i.v.-Arginine-provocationtest; in 7 cases GH-peaks did not rise over 10 ng/ml, 4 of the children showed GH-peaks of less than 4 ng/ml. One of the boys was treated with GH for 5 years with good results, no secondary effect on carbohydrate metabolism was observed. In one girl we started with GH-therapy only recently. In 7 of 9 children at the age of puberty we found hypogonadotrophic hypogonadism. In 10 patients, who underwent i.v. GTT, 4 showed a prediabetic metabolic state with elevated plasma insulin levels, a fifth boy suffered from diabetes. The development of type-2-diabetes is caused by abnormal insulin-resistance, which is connected with overfeeding and obesity. Treatment of obesity is the most important problem in the PLWS. Regular hypocaloric food is not accepted by most of the children. Therefore, in cases of ineffective dietetic treatment, we recommend gastric partitioning with proximal gastro-jejunostomy, as we performed in two of our patients with good results regarding weight-loss. In two of six children examined, we found chromosomal abnormalities.
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PMID:[Prader-Labhart-Willi syndrome]. 666 56

To investigate a possible hypothalamic alteration in obesity, we have studied the pattern of PRL secretion in response to insulin hypoglycemia, arginine infusion and TRH injection in 12 grossly obese patients and in 12 normal-weight controls. In the obese patients, PRL secretion was significantly lower than in normal subjects in response to insulin hypoglycemia and arginine infusion, while it was not significantly different from that in controls in response to TRH. The mean +/- SE values of the areas subtended by the PRL curves in the 3 above tests were 54.7 +/- 155.81 vs 3677.3 +/- 520.30 ng/2h, p less than 0,01, 210.3 +/- 148.93 vs 1034.8 +/- 203.15 ng/2h, p less than 0.05 and 1476.8 +/- 275.13 vs 2148.6 +/- 682.06 ng/2h, NS, respectively, in the obese and in controls. These results are compatible with the concept of impaired hypothalamic control of PRL secretion in obesity, although it is still unclear what role this may play in the pathogenesis of this disorder.
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PMID:Impaired prolactin secretion in obese patients. 679 62


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