Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[125I]Insulin binding to insulin receptors on circulating monocytes was studied in 9 patients with acromegaly associated with fasting hyperglycemia and was compared to previously reported studies of 11 patients with acromegaly who had normal or nearly normal glucose tolerance and 29 normal volunteers. In the hyperglycemic acromegalic, as had been found in the normoglycemic acromegalic, the total receptor concentration per cell was decreased in proportion to the hyperinsulinemia, i.e. the receptor concentration was inversely related to the basal level of insulin, similar to what is found in patients with obesity, diabetes, and insulin-secreting tumors. However, the acromegalic patients with hyperglycemia failed to show the increase in affinity of the empty receptor that had previously been found in their normoglycemic counterparts. The failure to increase receptor affinity causes the cells of the hyperglycemic acromegalic patients to bind less insulin at each insulin concentration than do the cells of normoglycemic patients. Again, the abnormalities in the patients correlates very closely with abnormalities at the level of the insulin receptor, though the sequence of the molecular events that produce these changes remains to be determined.
 ...
PMID:Insulin receptor on monocytes from patients with acromegaly and fasting hyperglycemia. 633 36

The HAIR-AN syndrome that consists of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) is an underdiagnosed endocrinopathy, because hyperandrogenic women are not commonly screened for insulin resistance or acanthosis nigricans. The distinct pathophysiologic features of the HAIR-AN syndrome are discussed in detail. In this syndrome, the primary pathophysiologic derangements are the insulin resistance and the hyperandrogenism. The acanthosis nigricans is an epiphenomenon of these primary processes. In patients with the HAIR-AN syndrome, the degree of severity of the insulin resistance is positively correlated with the degree of severity of the hyperandrogenism. In patients with adequate pancreatic beta-islet cell reserve, insulin resistance results in a long-term increase in circulating insulin levels. The hyperinsulinemia probably directly stimulates ovarian androgen production. In turn, hyperandrogenism itself produces insulin resistance. This positive feedback loop between insulin resistance and hyperandrogenism propagates the disease, and increases its severity over time. The relationship between insulin resistance and hyperandrogenism may explain the hyperandrogenemia seen in the following disease processes: obesity, acromegaly, lipoatrophic diabetes, leprechaunism, and Kahn types A and B insulin resistance.
 ...
PMID:Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: a common endocrinopathy with distinct pathophysiologic features. 635 20

The authors reviewed 102 cases of bilateral renal enlargement seen on excretory urography (excluding hydronephrosis and duplex kidneys) to determine the clinical significance of this finding. Associated abnormalities were found in 48 patients, including diabetes mellitus in 29; nondiabetic obesity, large body structures, or chronic steroid use in 16; acromegaly in 1; and unknown etiology in 37, 2 of whom were found to have diabetes five years later. Because of the striking preponderance of diabetes in this study, a fasting blood glucose analysis is recommended for patients with unexplained bilateral renal enlargement on excretory urography.
 ...
PMID:Diabetes mellitus: the predominant cause of bilateral renal enlargement. 648 64

The interaction of insulin with its receptor represents one of the key intermediate steps between secretion of insulin and its final biologic effects. Alterations in this interaction have been found in a number of disease states, including obesity, non-insulin-dependent diabetes mellitus (NIDDM), glucocorticoid excess, and acromegaly, as well as several rare forms of severe insulin resistance. The major factor regulating the receptor in obesity and NIDDM appears to be insulin. In obesity this alteration in normal regulation occurs secondary to overeating, whereas in the diabetic state the nature of the primary defect is uncertain. The role of the receptor in insulin resistance and methods for its evaluation are discussed.
 ...
PMID:Role of insulin receptors in insulin-resistant states. 699 Jan 80

The clinico-hormonal course of acromegaly and the presence of the hyperlipemic syndrome were studied in relation to age, sex, associated hypothyroidism, diabetes, obesity and cardiovascular and atherosclerotic complications in 43 acromegalic patients (18 males and 25 females) of which 6 had received no treatment and 37 had been submitted 2 - 13 years to conventional roentgentherapy (31 cases), 90Y (5 cases) and hypophysectomy (1 case). Hyperlipemia (HLP), present in 24 acromegalic patients (55.8% of the cases) unrelated to age, was more frequent in women (64% as against 44% in males) and correlated with the clinico-hormonal evolution (GH greater than 20 mg) (60% of the cases), and associated hypothyroidism (79%), obesity (42%) and diabetes (25%). Of the hyperlipemic acromegalic patients, 62% had cardiovascular and atherosclerotic complications. The results of the study point to the need for a hypoglucidic, hypolipidic and associated treatment for hypothyroidism, diabetes and obesity in the prophylaxis of acromegalic atherosclerosis.
 ...
PMID:The dyslipemic syndrome in acromegaly. 704 Dec 36

Individual features of the endocrine system were studied in 26 healthy men, divided into 2 groups, according to the characteristics of EEG, electrocutaneous thresholds and the time response (TR) upon sound signals of 40 to 120 decibels. The subjects of the 1st group were characterized by the high energy of EEG delta- and theta-rhythms, low energy of alpha-rhythm, low thresholds and TR40 : TR120 ratio. The patients of the 2nd group had the opposite parameters. In both groups the blood plasma and urine catecholamine content, ACTH, TTH, 11-hydroxycorticosteroids, cortisol, aldosterone, thyroxine, triiodothyronine, testosterone and plasmatic insulin were determined by means of spectrofluorometry and radioimmunoassay. The elevation of the cortisol level after ACTH injection and of the TTH concentration following thyroliberin administration were investigated. Two polar variants of the endocrine system organization were revealed. The patients of the 1st group had an elevated activity of the sympathico-adrenal, hypophyseal-adrenal system and insular apparatus, comparatively lowered activity of the hypophyseal-thyroid system and gonads. The subjects of the 2nd group demonstrated an opposite character of the endocrine system. It is suggested that the individual peculiarities of the human endocrine system promote the development of obesity, Icenko-Cushing's disease, hypertension, thyrotoxicosis, acromegaly and bronchial asthma.
 ...
PMID:[Individual characteristics of the organization of the human endocrine system]. 712 44

This prospective study defines the clinical and biochemical features of acromegaly in a large cohort of patients. There was no difference in sex distribution, and for men and women the mean ages at diagnosis (40 +/- 12 and 40 +/- 14 yr, respectively) were similar. Nearly three-quarters of patients were overweight and some 12% severely overweight; the frequency and severity of obesity also was not different between the sexes. Half of patients were hypertensive or were taking anti-hypertensive drugs. Neither GH nor insulin levels were significantly different between normotensive and hypertensive patients. Acral growth and facial coarsening, soft tissue swelling, and excessive perspiration were present in the majority (98%) of patients. Mean serum GH, Sm-C, and PRL levels did not differ between the sexes. Sm-C levels correlated with mean GH concentration (r = 0.31, p < 0.001), both variables inversely related to age. With each decade of life, mean GH and Sm-C levels declined by 7.6 +/- 0.2 ng/mL and 0.5 +/- 0.2 U/mL, respectively. Impaired glucose tolerance was diagnosed in 36% and frank diabetes mellitus in 30% of patients. Hyperprolactinemia was noted in 18% of patients. Galactorrhea was noted in 43 (9%) patients, most of whom were female; the mean GH levels of patients with galactorrhea (60.1 +/- 13 ng/mL) were higher than those of patients without (35.4 +/- 2.6 ng/mL, p = 0.02). Acromegaly appears to afflict men and women equally with a preponderance of presentation in the fourth decade of life.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Acromegaly. Clinical and biochemical features in 500 patients. 793 7

Plasma glucose and serum insulin during OGTT were measured in 33 patients with essential hypertension, 17 patients with simple obesity, 19 patients with acromegaly and 10 normal adults. Compared with control, serum insulin concentration increased in 33 patients with essential hypertension at 3 hour postload (P < 0.05) and in 17 patients with simple obesity at 1 hour postload (P < 0.05) during OGTT, 19 patients with acromegaly also had their insulin concentration increased at 1.3 hour postload (P < 0.05) during OGTT. The correlationships between diastolic blood pressure and integrated area under the curve for serum insulin concentration (r = 0.3838, P < 0.05) were observed in 33 patients with essential hypertension. Serum insulin concentration decreased in 10 patients with essential hypertension at 1 and 2 hour postload during OGTT after antihypertensive treatment with captopril or captopril plus hydrochlorothiazide. The results indicated that the patients with essential hypertension, simple obesity and acromegaly are insulin resistant and hyperinsulinemic after an oral glucose load.
 ...
PMID:[A preliminary study of insulin resistance in essential hypertension, simple obesity and acromegaly]. 820 Mar 5

Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration: in fact, prolonged administration of GHRPs increases IGF-1 levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and decreases thereafter. By the sixth decade of life, the activity of GHRPs is reduced but it is still marked and higher than that of GHRH. The GH-releasing activity of GHRPs is synergistic with that of GHRH, is not affected by opioid receptor antagonists, such as naloxone, and is only blunted by inhibitory influences, including neurotransmitters, glucose, free fatty acids, gluco corticoids, recombinant human GH and even exogenous somatostatin, which are known to almost abolish the effect of GHRH. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states such as in acromegaly, anorexia nervosa and hyperthyroidism. On the other hand, their good GH-releasing activity has been shown in some but not in other somatotrope hyposecretory states. In fact, reduced GH responses after GHRP administration have been reported in idiopathic GH deficiency as well as in idiopathic short stature, in obesity and in hypothyroidism, while in patients with pituitary stalk disconnection or Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. In short children an increase in height velocity has also been reported during chronic GHRP treatment. Thus, based on their marked GH-releasing effect even after oral administration, GHRPs offer their own clinical usefulness for treatment of some GH hyposecretory states.
 ...
PMID:Growth hormone-releasing peptides. 918 61

Growth hormone-releasing peptides (GHRPs) are a series of hepta (GHRP-1)- and hexapeptides (GHRP-2, GHRP-6, Hexarelin) that have been shown to be effective releasers of GH in animals and humans. More recently, a series of nonpeptidyl GH secretagogues (L-692,429, L-692,585, MK-0677) were discovered using GHRP-6 as a template. Some cyclic peptides as well as penta-, tetra-, and pseudotripeptides have also been described. This review summarizes recent developments in our understanding of the GHRPs, as well as the current nonpeptide pharmacologic analogs. GHRPs and their analogs have no structural homology with GHRH and act via specific receptors present at either the pituitary or the hypothalamic level. The GHRP receptor has recently been cloned and it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. Although the exact mechanism of action of GHRPs has not been fully established, there is probably a dual site of action on both the pituitary and the hypothalamus, possibly involving regulatory factors in addition to GHRH and somatostatin. Moreover, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. The marked GH-releasing activity of GHRPs is reproducible and dose-related after intravenous, subcutaneous, intranasal, and even oral administration. The GH-releasing effect of GHRPs is the same in both sexes, but undergoes age-related variations. It increases from birth to puberty and decreases in aging. The GH-releasing activity of GHRPs is synergistic with that of GHRH and not affected by opioid receptor antagonists, while it is only blunted by inhibitory influences that are known to nearly abolish the effect of GHRH, such as neurotransmitters, glucose, free fatty acids, glucocorticoids, rhGH, and even exogenous somatostatin. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states, such as acromegaly, anorexia nervosa, and hyperthyroidism. On the other hand, GHRPs and their analogs have been reported to be effective in idiopathic short stature, in some situations of GH deficiency, in obesity, and in hypothyroidism, while in patients with pituitary stalk disconnection and in Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. A potential role in the treatment of short stature, aging, catabolic states, and dilated cardiomyopathy has been envisaged.
 ...
PMID:Growth hormone-releasing peptides and their analogs. 946 89


<< Previous 1 2 3 4 5 6 7 8 Next >>