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

Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate the function of hypothalamic GHRH and somatostatin and of pituitary receptors for these neurohormones as assessed by the effectiveness of GHRH and somatostatin on adenylate cyclase (AC) activity. Baseline GH secretion of pituitaries obtained from male and female obese rats was not different and similar to that present in lean counterparts. Stimulation with 10(-7) M GHRH elicited a significantly lower GH secretion from the pituitaries of obese male rats but induced a similar GH secretion from the pituitaries of lean and obese female rats. In these pituitaries, GH concentration was similar in obese versus lean male and female rats [corrected]. A sex-related difference was also evidenced when plasma concentrations of somatomedin C (IGF-I) were evaluated. Obese male rats had lower IGF-I concentrations than lean counterparts, while this was not the case for obese versus lean female rats. Evaluation of AC activity following GHRH disclosed a lower activation in obese than in lean male rats, whereas in the females the enzyme activation was higher in obese than in lean animals. Conversely, the inhibitory effect of somatostatin on forskolin-stimulated AC was similar in pituitary membranes of obese and lean rats of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone secretion is differently affected in genetically obese male and female rats. 810 99

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

Thyrotropin releasing hormone (TRH) administration is known to induce a greater TSH response in normal subjects than in obese subjects. In obesity even GH and PRL response to various stimuli are blunted, presumably because of an augmented somatostatinergic tone in obese subjects. Further studies have shown that pyridostigmine (Pyr), an acetylcholinesterase inhibitor, is capable of augmenting GH in obesity by means of somatostatin inhibition. In order to evaluate the possible interference of an increased somatostatinergic tone on TSH secretion, we studied the TSH response to a TRH bolus in 5 obese children with or without a pyr pretreatment. Similarly, we tested a group of 10 obese adult subjects, with TRH alone or TRH plus pyr administration, 30 min or 60 min before TRH. All subjects had a body weight of 30-50% greater than I.B.W. Our data show that a pretreatment with pyr, 60 min before TRH administration, significantly augments the TSH response in adult obese subjects but not in children; the modality of pyr administration seems to be crucial to evidenciate such an alteration since the pyr pretreatment is not effective when administered 30 min before TRH. The absence of this pyr effect in obese children induces to hypothesize that somatostatinergic tone is differentially modulated in children vs adult obese subjects.
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PMID:Pyridostigmine effects on TSH response to TRH in adult and children obese subjects. 834 46

Plasma glucose and insulin responses to oral glucose and insulin-mediated glucose disposal were determined in 20 patients with microvascular angina and 20 normal volunteers who were similar in terms of age, gender distribution, and degree of obesity. Plasma glucose and insulin responses to a 75-g oral glucose challenge were significantly higher in those with microvascular angina (P < .001), as were steady-state plasma glucose concentrations after a 180-minute infusion of somatostatin, glucose, and insulin (12.2 +/- 1.0 v 7.6 +/- 0.6 mmol/L, P < .001). Since steady-state plasma insulin concentrations were similar in the two groups (627 +/- 32 v 631 +/- 29 pmol/L), these data indicate that patients with microvascular angina are insulin-resistant, glucose-intolerant, and hyperinsulinemic compared with a matched group of normal volunteers.
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PMID:Insulin resistance, glucose intolerance, and hyperinsulinemia in patients with microvascular angina. 841 59

It is known that spontaneous and stimulated GH secretion is reduced in obesity. On the other hand, it has been recently reported that, in obese subjects, plasma GH levels did not change during a hyperglycemic clamp. To further study the sensitivity of somatotrope cells to inhibitory influences in obesity, we studied the effect of somatostatin, pirenzepine, or glucose on the GH response to GHRH or arginine in 32 obese patients and 30 controls. Basal GH levels were lower in obese than in normal subjects (1.0 +/- 0.6 vs. 4.8 +/- 0.7 micrograms/L, P < 0.05), while insulin-like growth factor-I levels were similar in both groups (137.3 +/- 13.2 vs. 138.8 +/- 12.2 micrograms/L). In obese as well as in control subjects pirenzepine abolished the GH response to either GHRH (AUC0-120: 43.7 +/- 9.6 vs. 258.3 +/- 59.9 micrograms/L/h, P < 0.04 and 113.0 +/- 75.0 vs. 870.5 +/- 255 micrograms/L.h, P < 0.01, respectively) or arginine (6.5 +/- 2.5 vs. 118.7 +/- 55.9 micrograms/L.h, P < 0.05 and 47.7 +/- 7.3 vs. 334.0 +/- 157.5 micrograms/L.h, P < 0.01, respectively). Differently from pirenzepine, glucose blunted the GH response to either GHRH or arginine in control subjects (260.8 +/- 38.3 vs. 479.5 +/- 83.9 micrograms/L.h, P < 0.03 and 294.8 +/- 46.3 vs. 625.1 +/- 139.1 micrograms/L.h, P < 0.05, respectively), but failed to modify it in obese patients (193.7 +/- 39.4 vs. 172.4 +/- 33.6 micrograms/L.h and 121.1 +/- 43.4 vs. 155.1 +/- 39.7 micrograms/L.h, respectively). On the other hand, somatostatin deeply blunted the GHRH-induced GH release in obese patients (58.5 +/- 25.4 vs. 548.7 +/- 196.6 micrograms/L.h, P < 0.05) as well as in controls (181.4 +/- 44.4 vs. 759.7 +/- 46.6 micrograms/L.h, P < 0.04). In conclusion, our results show that, in obesity, the stimulated GH release is refractory to the inhibitory effect of glucose but not of pirenzepine, in spite of their likely common mechanism of action, i.e. increase of hypothalamic somatostatin release. Exogenous somatostatin is able to abolish GH secretion both in normal and obese subjects. These data suggest the existence of a peculiar inhability of hyperglycemia to trigger somatostatinergic release in obesity.
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PMID:In obesity the somatotrope response to either growth hormone-releasing hormone or arginine is inhibited by somatostatin or pirenzepine but not by glucose. 853 Jun 34

The current study was undertaken to examine the impact that obesity and non-insulin-dependent diabetes mellitus (NIDDM) have on the ability of glucose to stimulate its own uptake and oxidation in muscle. Euglycemic and hyperglycemic clamp experiments were performed with somatostatin infusions so that insulin could be replaced to basal levels or to physiological hyperinsulinemia. Arteriovenous leg balance methods were used to measure the pathways of leg muscle glucose uptake, oxidation, and storage. Percutaneous biopsies of the vastus lateralis muscle were taken to determine the pyruvate dehydrogenase complex or glycogen synthase activities. During basal insulin replacement, obese compared with lean nondiabetic subjects had higher values for glucose uptake, respiratory quotient, and glucose oxidation (all P<0.05) and a higher proportion of leg energy expenditure derived from glucose. Obese NIDD patients had a greater reliance on fat calories than lean diabetics during basal insulin replacement (P< 0.05). Hyperinsulinemia increased leg glucose metabolism (P<0.001) in all groups, but obese NIDD patients were significantly more insulin resistant. Hyperglycemia in NIDDM compensated for insulin resistance to the extent that rates of glucose metabolism were the same as those for nondiabetics studied at euglycemia. When nondiabetics were studied at hyperglycemia matched to the diabetics, the insulin resistance was still readily apparent.
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PMID:Interaction of carbohydrate and fat fuels in human skeletal muscle: impact of obesity and NIDDM. 863 94

Suppression of hepatic glucose output (HGO) has been shown to be primarily mediated by peripheral rather than portal insulin concentrations; however, the mechanism by which peripheral insulin suppresses HGO has not yet been determined. Previous findings by our group indicated a strong correlation between free fatty acids (FFA) and HGO, suggesting that insulin suppression of HGO is mediated via suppression of lipolysis. To directly test the hypothesis that insulin suppression of HGO is causally linked to the suppression of adipose tissue lipolysis, we performed euglycemic-hyperinsulinemic glucose clamps in conscious dogs (n = 8) in which FFA were either allowed to fall or were prevented from falling with Liposyn plus heparin infusion (LI; 0.5 ml/min 20% Liposyn plus 25 U/min heparin with a 250 U prime). Endogenous insulin and glucagon were suppressed with somatostatin (1 microgram/min/kg), and insulin was infused at a rate of either 0.125 or 0.5 mU/min/kg. Two additional experiments were performed at the 0.5 mU/min/kg insulin dose: a double Liposyn infusion (2 x LI; 1.0 ml/min 20% Liposyn, heparin as above), and a glycerol infusion (19 mg/min). With the 0.125 mU/min/kg insulin infusion, FFA fell 40% and HGO fell 33%; preventing the fall in FFA with LI entirely prevented this decline in HGO. With 0.5 mU/min/kg insulin infusion, FFA levels fell 64% while HGO declined 62%. Preventing the fall in FFA at this higher insulin dose largely prevented the fall in HGO; however, steady state HGO still declined by 18%. Doubling the LI infusion did not further affect HGO, suggesting that the effect of FFA on HGO is saturable. Elevating plasma glycerol levels did not alter insulin's ability to suppress HGO. These data directly support the concept that insulin suppression of HGO is not direct, but rather is mediated via insulin suppression of adipose tissue lipolysis. Thus, resistance to insulin control of hepatic glucose production in obesity and/or non-insulin-dependent diabetes mellitus may reflect resistance of the adipocyte to insulin suppression of lipolysis.
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PMID:Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. 869 66

Obesity is coupled to several disturbances of the endocrine axes. It has previously been shown that genetically obese Zucker male rats have an impaired secretion of growth hormone (GH), probably originating from a primary reduction of hypothalamic GH-releasing hormone (GHRH) function and resulting in a decrease of GH gene expression and release. We sought to evaluate the somatotropic function in another model of experimental obesity. Normal male Sprague-Dawley rats were fed an energy-rich highly palatable diet for 7 months until they reached body weights overlapping those reported for obese Zucker rats. They were then evaluated for different indices of the hypothalamo-pituitary-somatomedin-C (IGF-I) axis. At the end of the overfeeding period, rats were divided into overtly obese (obese group) and overweight (overweight group) rats according to the degree of overweight and the Obesity Lee Index, while rats fed ad libitum with the standard pellet chow served as controls. Acute administration of a supramaximal dose of GHRH (2 micrograms/rat i.v.) elicited a significantly (at least P < 0.05) lower plasma GH rise in the overweight and obese groups compared with the controls although no difference was seen in the pituitary GH content and gene expression and plasma concentrations of free IGF-I in the two experimental groups vs the controls. In addition, evaluation of hypothalamic GHRH and somatostatin mRNAs (slot-blot hybridization) did not show any significant differences between the three groups. Of the different metabolic indices investigated, plasma glucose and insulin concentrations were significantly (P < 0.01) higher in the obese than in the overweight and control groups. A sharp decrease in plasma testosterone levels, together with a reduction in testis weight, was seen in both groups of rats fed the palatable diet compared with the controls. These findings underline the 'peripheral' feature of the hyposomatotropinism of rats chronically fed an energy-rich diet, and may account for the reversibility of the GH impairment in many obese subjects once a normal body weight has been restored. Moreover, the peripherally-driven hyposomatotropinism of these rats is in sharp contrast with the hypothalamic-driven GH secretory impairment of the obese Zucker rats.
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PMID:Characterization of the hypothalamo-pituitary-IGF-I axis in rats made obese by overfeeding. 869 49

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.
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PMID:Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies. 876 5

To challenge the view that resistance to insulin-mediated glucose uptake in noninsulin-dependent diabetes mellitus (NIDDM) is limited to patients with microalbuminuria, high blood pressure, or obesity, we compared measurements of insulin resistance in 29 normal volunteers and 31 normotensive patients with NIDDM (mean +/- SE fasting plasma glucose, 160 +/- 10 mg/dL). The patients with NIDDM were nonobese (body mass index, < 27 kg/m2), with urinary albumin excretion (UAE) less than 20 micrograms/min on the basis of two overnight urine collections. The two groups were similar in age and body mass index. Although patients with NIDDM had neither high blood pressure nor microalbuminuria; both their blood pressure (125 +/- 2/79 +/- 1 vs, 113 - 2/73 +/- 2 mm Hg) and UAE excretion (4.7 +/- 0.58 vs. 2.12 +/- 0.17 micrograms/min) were somewhat higher than those in the control population. Resistance to insulin-mediated glucose disposal was quantified by measurement of the steady state plasma glucose (SSPG) and insulin (SSPI) concentrations during the last 30 min of an 180-min infusion of somatostatin (5 micrograms/min), insulin (25 mU/min-m2), and glucose (240 mg/min-m2). The results showed that SSPI concentrations were similar in the two groups (64 +/- 3 vs. 62 +/- 3 microU/mL), but SSPG concentrations were approximately twice as high in patients with NIDDM (258 +/- 15 vs. 139 +/- 11 mg/dL;P < 0.001); demonstrating the presence of severe insulin resistance. Furthermore, the magnitude of the differences in the SSPG values of the two groups did not change and remained highly significant when adjusted for small differences in age, body mass index, blood pressure, and UAE. Finally, SSPG did not correlate with age, body mass index, blood pressure, or UAE in either group. These data again demonstrate that insulin resistance exists in patients with NIDDM, and that this defect is present in the absence of obesity, high blood pressure, or microalbuminuria.
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PMID:Resistance to insulin-mediated glucose disposal in patients with noninsulin-dependent diabetes mellitus in the absence of obesity or microalbuminuria--a Clinical Research Center study. 877 92


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