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

Obese Zucker rats were either pair-fed to their lean litter-mates or fed ad lib, to determine the effect of hyperphagia on serum hormone levels and tissue metabolism as indicated by enzyme activities and in vitro metabolite flux. Hyperphagia was shown to be non-essential for the elevation in serum insulin and suppression in serum growth hormone and prolactin in the genetically obese rat. It was also shown that the increased liver cell lipogenic rate was not dependent on hyperphagia in the obese rat and that adipose cell lipogenesis was not significantly altered in the pair-fed obese rat. The utilization of alanine for glucose synthesis in vitro was similar for both lean and obese rats, but its utilization for fatty acid synthesis was higher in the obese rat. Data is presented which suggest that the inhibitory effect of glucagon on liver lipogenesis is blunted in the obese rat.
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PMID:Serum hormone levels and tissue metabolism in pair-fed lean and obese Zucker rats. 19 81

Insulin resistance may occur to a variable degree in various disease conditions. Obesity is frequently accompanied by insulin resistance. The anti-insulin antibodies in patients treated with insulin are a classical cause, but in fact rare. Insulin resistance of variable degree may accompany certain metabolic disorders, e.g. diabetic ketosis and acidosis, and endocrine disorders, e.g. Cushing's syndrome, acromegaly. The measurement of insulin receptors brings a new dimension to the investigation of insulin resistance. Insulin receptors are reduced in number during obesity. The abnormality, partly responsible for insulin resistance, is reducible by reduction in calory intake. Circulating insulin anti-receptor antibodies appear to be responsible for insulin resistance which is particularly marked although exeptional, in nonobese diabetics with acanthosis nigrans and auto-immune symptoms.
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PMID:[New data in the domain of insulin resistance]. 19 31

Several characteristics of the binding of insulin and glucagon to human circulating mononuclear leukocytes have been studied. Functional analysis (latex bead ingestion) revealed that cell mixtures, as prepared according to Boyum and used generally in studies of insulin resistance in humans, consist of 20-29% phagocytic monocytes, with the remainder being lymphocytes. Partial separation of monocytes from lymphocytes on columns of Sephadex G-10, followed by correlation of insulin binding with cell type, confirms that the monocyte is the binding species. Insulin influenced neither glucose uptake nor the further conversion of glucose to lipids and CO2 by the leukocytes. The transport of alpha-aminoisobutyrate, a nonmetabolizable amino acid, into these cells was also unaffected by insulin. Monocyte/lymphocyte mixtures specifically bound glucagon and prostaglandin E1. At physiological concentrations of these hormones, steady states were reached in 15 min and 45 min, respectively. In contrast to the 8-10-fold increases in cellular cyclic AMP produced by prostaglandins, the effect of glucagon was very small but apparently real. Under appropriate preincubation conditions, sodium azide and iodoacetamide inhibited phagocytosis and insulin binding in parallel. The binding of glucagon was unaffected by these agents. Although both antimycin A and actinomycin D inhibited phagocytosis of the monocytes, only the former inhibited insulin binding; there was only a slight effect on glucagon binding. We would conclude that the binding of insulin to human circulating monocytes, although reflective of insulin resistance in diabetes mellitus and obesity, may not be to traditional receptors. In contrast, the binding of glucagon to lymphocyte/monocyte mixtures may be to function-linked receptors.
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PMID:Hormone receptors: VI. On the nature of the binding of glucagon and insulin to human circulating mononuclear leukocytes. 20 May 11

To get some insight into the mechanisms of insulin resistance in obesity, insulin binding and biological effects were investigated in soleus muscles isolated from normal and obese mice. Basal and insulin-stimulated 2-deoxyglucose uptake were measured at the steady state of insulin binding. The results were consistent with the concept of spare receptors, i.e., maximal insulin effect was achieved when only about 20% of total receptors was occupied. When similar studies were applied to muscles of gold thioglucose obese or genetically obese (ob/ob) mice, and compared to lean controls: a) insulin binding was decreased; b) the insulin dose-response curve of 2-deoxyglucose uptake was shifted to the right; c) maximally insulin-stimulated 2-deoxyglucose uptake, glycolysis, and glycogen synthesis were markedly decreased. Insulin binding and effects returned toward normal after a 40-h fast in obese mice. These results point to two loci for the insulin resistance of skeletal muscle in obesity: 1) a decrease in the number of insulin receptors, which results in a diminished insulin sensitivity; and 2) one or more alterations beyond receptor that are responsible for the decreased responsiveness of the tissue to insulin and appear to play a major role in the insulin resistance of muscle in obesity.
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PMID:Insulin binding and effects in isolated soleus muscle of lean and obese mice. 20 48

At present the two different mechanisms underlying the hypertriglyceridemia of diabetes are reasonably well defined. The rationale of therapy has grown from this knowledge. One form of hyperlipidemia is due to the hyperinsulinemia which results from the patient's resistance to insulin. The approach to treatment aims to overcome the insulin resistance. In most patients this is done by treating their obesity. The other form of hypertriglyceridemia results from insulin deficiency and is treated by bringing the patient's diabetes under control. There is strongly suggestive evidence that hypertriglyceridemia may be associated with a high risk of atherosclerosis. The reason for treating hypertriglyceridemia in general, and in the diabetic in particular, is to reduce this risk. However, it must be conceded that, at the moment, there is no information about the effect of lower triglyceride levels on the incidence of atherosclerosis. Hence much epidemiologic research is needed before our rationale for treatment can move from the realm of hope to the realm of definite proof. In the mean time an attack on this and the other risk factors is the best way we have to attempt to prevent the major complication of diabetes, atherosclerosis.
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PMID:Hyperlipidemia, atherosclerosis, and diabetes. 20 21

Pancreatic Polypeptide (PP) was first described in birds by Kimmel et al. (1968). It was later isolated from the pancreas of several mammalian species by Chance and Jones (1974). It has been demonstrated in the islets of many animal species by immunocytochemical methods. PP levels are assayable in plasma and rise sharply after food intake. The pharmacological properties and physiological role of PP are still ill defined. It appears to have a spectrum of actions peculiar to each species. Recent research on this subject is reviewed in this article. High levels of circulating PP have been demonstrated in juvenile and maturity-onset diabetics, as well as in some patients with islet cell tumors. However no definite clinical syndrome due to hypersecretion of PP as been identified as yet. It remains a matter of speculation that a deficiency of PP might be responsible for some types of obesity. PP-cells are rare in the pancreas of healthy young individuals. Hyperplasia of PP-cells has been observed in a wide variety of pathological conditions, but is most prominent in the pancreas of chronic insulin dependent diabetics. Histologic evidence strongly suggests that PP-cell hyperplasia represents an atypical form of islet regeneration. It is always focal in distribution and is most remarkable in those lobules that have lost the capacity to reproduce islets of normal cytologic composition.
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PMID:[Pancreatic polypeptide (author's transl)]. 21 73

The effects of hormones on human adipose tissue are reviewed with respect to the pathogenesis, prevention and therapy of obesity. Insulin. The insulin-resistance in the obese is associated with a decrease of the number of insulin receptor sites, which is likely to be secondary to increased insulin levels. Catecholamines. Human adipose tissue contains alpha- and beta-adrenergic receptors. Alterations in the relation of alpha- and beta-adrenergic responsiveness may be important in the pathogenesis of regional forms of obesity. Gastrointestinal hormones. As opposed to adipose tissue of other species lipolytic effects of gastrointestinal hormones were as yet not clearly demonstrated in human fat cells. Prostaglandins were implicated in the pathogenesis of metabolic obesity. However, the effects of these C-20 fatty acids on human adipose tissue remain to be elucidated. Parathyroid hormone has been shown to possess lipolytic activity in vitro. This property may be important under physiological conditions too. Triglyceride storage diseases and lipomatoses are discussed as models for studying impaired hormonal responsiveness in human adipose tissue.
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PMID:[Obesity and adipose tissue. 2. Hormonal regulation of adipose tissue metabolism]. 21 12

Previous studies have shown that the sensitivity of tissues to insulin is diminished in states of glucocorticoid and GH excess and is increased when these hormones are deficient. To evaluate the role of the insulin receptor in these states, we have studied [125I]insulin binding to purified liver plasma membranes obtained from rats with a variety of perturbations of both glucocorticoids and GH. Glucocorticoid excess was produced in rats by administration of ACTH (40 U/day for 4 days) or dexamethasone (1 mg/day for 4 days). This resulted in an insulin-resistant state. Associated with this insulin resistance, there was a 50-60% decrease in insulin binding to its specific receptors in liver. Conversely, adrenalectomy, which produces an increase in insulin sensitivity, was associated with an increase in insulin binding to liver. Computer-assisted Scatchard analysis using a negative cooperative model for the inulin-receptor interaction indicated that, in contrast to our findings with obesity, the changes in insulin binding in these states were most likely due entirely to changes in receptor affinity, with no change in receptor concentration. GH administration also produced mild insulin resistance and a decrease in receptor concentration. This was associated with a reciprocal increase in receptor affinity and thus, no major alteration in insulin binding occurred at low physiological insulin concentrations. Hypophysectomized rats, on the other hand, showed an increase in receptor concentration and a decrease in affinity, and GH treatment only partially corrected these changes. Rats implanted with the MtT tumor (which secretes ACTH, GH, and PRL) have the combined effects of excess glucocorticoids and GH and are very insulin resistant. Liver membranes prepared from these rats showed a decrease in insulin binding and receptor affinity similar to that observed in other states of glucocorticoid excess. Further, adrenalectomy of the tumor-bearing rats resulted in an increase in insulin binding despite the persistence of the elevated levels of GH, ACTH, and PRL. These findings suggest that alterations in insulin receptor affinity and number may play a major role in the states of altered insulin sensitivity which accompany glucocorticoid excess and deficiency, and follow hypophysectomy. In contrast, the insulin resistance associated with GH excess is mediated at either a site on the receptor distal to the insulin-binding site (i.e. transduction) or at one or more of the intracellular reactions important in insulin action.
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PMID:Alterations in insulin binding induced by changes in vivo in the levels of glucocorticoids and growth hormone. 21 65

The common obesity of middle age presents a set of features that strongly resembles the cardinal symptoms of Cushing's syndrome: obesity of the face (moon face), upper back (buffalo hump) and trunk (pot belly) accompanied by signs of protein-wasting. In non-obese individuals who remain at a constant weight throughout life, the proportion of adipose tissue increases with age at the expense of lean tissue loss. Thus, a mild version of Cushing's syndrome may be part of the normal aging process. A more intense version of this process may occur in overweight adults. Excess and chronic activity of two pituitary hormones may contribute to this adiposity. Both hormones are produced in the same pituitary cell by cleavage from a common large precursor known as pro-opiocortin. One hormone is adrenocorticotrophin (ACTH), which stimulates the release of the glucocorticoid hormones. These hormones promote the conversion of bodily proteins to glucose (gluconeogenesis). The other pituitary hormone is beta-endorphin, a stimulant of appetite that causes the release of insulin. This pancreatic hormone promotes the conversion of glucose and fatty acids to triglycerides (lipogenesis). Three different etiologies are suggested for the excessive and chronic action of these two pituitary hormones: tumors that increase the number of cells that synthesize pro-opiocortin; mutant strains that produce excessive amounts of ACTH and beta-endorphin such as the genetically obese mouse (ob/ob) and rat (fa/fa); and an age-determined shift in the type of cleavage enzymes present in the pro-opiocortin cell that favors ACTH and beta-endorphin production.
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PMID:The obesity of middle age: a common variety of Cushing's syndrome due to a chronic increase in adrenocorticotrophin (ACTH) and beta-endorphin activity. 22 74

The authors report a girl with acute lymphoblastic leukaemia presenting hypothalamic syndrome characterized by meningeal leukaemia, hyperphagia and obesity. Insulin and growth hormone secretion, studied with arginine and insulin stimulation tests, showed a high peak of serum insulin and no response of growth hormone. Insulin and growth hormone responses to these tests reverted to normal after intrathecal methotrexate.
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PMID:Insulin and growth hormone secretion in a leukaemic girl with hypothalamic syndrome. 26 33


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