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

The Zucker (fatty) rat is one of a group of animals that inherit obesity as an autosomal Mendelian recessive trait. These rats are obese, hyperphagic, and hyperinsulinemic, but blood glucose remains at normal levels. Although these rats eat more than normal rats, their response to the addition of adulterants to the food or after exposure to the cold is more like that of normal rats than rats with hypothalamic obesity. The hypertriglyceridemia which characterized these animals is due to the increased hepatic production of a very low density lipoproteins. Adipocytes are increased in size and in number with the subcutaneous fat depot showing the largest increase in the number of fat cells. Lipogenesis from glucose is brisk in the young animals but declines with age. Enzymatic patterns of glycolysis and gluconeogenesis appear to reflect the altered internal milieu rather than specific defects. Endocrine changes in the fatty rat include hyperinsulinemia, reduced levels of glucagon, hypothyroidis, and impaired reproductive function. A model is presented in which the features of the genetically obese (Zucker) fatty rat are compared with those of animals with hypothalamic obesity.
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PMID:The Zucker-fatty rat: a review. 32 51

A patient with obesity and diabetes mellitus had insulin secretion studies done during a 3-year cycle of weight loss and regain in the course of which she progressed from frank diabetes to a normal state of carbohydrate tolerance and then back to her original diabetic state. The results suggest that therapeutic weight reduction not only reverses insulin resistance but also restores beta cell sensitivity and enhances beta cell capacity. The eventual re-establishment of a degree of obesity, hyperinsulinemia, and carbohydrate intolerance virtually identical to that originally seen is compatible with a primary disorder involving hypothalamic control of adipose stores and insulin secretion.
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PMID:Insulin secretion in obesity and diabetes: an illustrative case. 33 68

A new strain of obese mouse, the PBB/Ld, has been studied in terms of fat pad cellularity, serum insulin and blood glucose levels, and response to gold thioglucose injections. Age-matched C57B1/6J mice were used as controls. Adipocyte size and number in the major fat depots were determined at various ages from weanling to maturity in the PBB/Ld and C57B1/6J strains. Results indicated that obesity in the PBB/Ld was due to hypertrophy of adipocytes in retroperitoneal and subcutaneous fat depots and to hypertrophy and hyperplasia in the epididymal fat pad. PBB/Ld mice also developed hyperinsulinemia and hyperglycemia and these findings have been discussed in terms of the developmental changes in fat pad cellularity. The injection of gold thioglucose led to increased food intake in both PBB/Ld and C57B1/6J mice. Hyperphagia was also present in the PBB/LD control group, but increased efficiency of converting calories to body weight was not observed in this group when compared to control C57B1/6J mice. The characteristics of obesity seen in the PBB/Ld mouse are discussed and comparisons are made to similar studies in other rodent models of obesity.
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PMID:Description of obesity in the PBB/Ld mouse. 34 7

It has been considered that hyperinsulinemia is one of the important factors in the development of obesity. With the purpose of investigating the mechanisms of hyperinsulinemia in obese rats induced by hypothalamic lesions (HTL), the time-caused changes in body weight, blood glucose and plasma immunoreactive insulin (IRI) levels in addition to histological changes in the pancreatic islet were studied. The following results were obtained. 1. The development of obesity, a rise of plasma IRI level and an enlargement of pancreatic islets were found in HTL rats. The enlargement of pancreatic islets was directly proportional to body weight, index of obesity and plasma IRI level. 2. The B cells of the pancreatic islets of HTL rats revealed well-developed Golgi apparatus and rough endoplasmic reticulum, and numerous degranulated and pale secretory granules. 3. A number of mixed cells were shown in the periphery of the pancreatic islets of HTL rats. 4. Emiocytotic phenomena of the granular discharge were encountered frequently in the B cells of the pancreatic islets of HTL rats. These histological findings of the B cells in HTL rats well reflected hypersecretion of insulin in this type of obesity.
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PMID:[Histological study of pancreatic islets in hypothalamic obese rats (author's transl)]. 36 46

A longitudinal in vivo and in vitro analysis of the genesis of insulin resistance has been carried out in mice made obese by chemical made obese by chemical lesion (goldthioglucose, GTG) of the hypothalamus. Six weeks after GTG administration, glycemia and glucose disposal were normal but associated with increased insulin concentration, suggesting incipient insulin resistance. The in vitro counterpart of the latter in obese mice was observed in soleus muscle that was somewhat less responsive to insulin than controls, in liver that had increased basal lipogenesis but was uninfluenced by insulin, and in hepatic plasma membranes in which a slight decrease of insulin binding was measured. At this stage of obesity, basal adipose tissue lipogenesis was increased but the tissue responded in a normal fashion to insulin. These relatively discrete early metabolic changes were corroborated in vivo by a normal hypoglycemic effect of exogenous insulin. Sixteen weeks after GTG administration, hyperglycemia and gross hyperinsulinemia were recorded. This insulin resistance was evidenced in vivo by the lack of hypoglycemic effect of exogenous insulin unless considerable amounts of the hormone were administered. It coincided in vitro with a poor response of soleus muscle to insulin, an absence of a stimulatory effect of the hormone upon both adipose tissue and liver tissue, and a marked decrease in insulin binding to liver plasma membranes. It appears that insulin resistance is a multifactorial and progressive abnormality that might involve both insulin receptor and intracellular metabolic alterations.
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PMID:Longitudinal study on the establishment of insulin resistance in hypothalamic obese mice. 36 21

Obesity in the Zucker rat is accompanied by hyperlipemia, hyperinsulinism, insulin resistance, pancreatic hyperplasia, and islet hypertrophy. This study correlates the morphologic heterogeneity of isolated pancreatic islets with secretion of insulin and glucagon in the perifusion system. Islet size was arbitrarily defined as large (greater than 0.45 mm) or small (smaller than 0.12 mm). Protein content and volume (V = 4/3pir3) were calculated for groups and individual islets, respectively. Islets from obese rats secreted more insulin in response to glucose and aminophylline than islets from lean rats (peak 7.8 +/- 2.4 vs. 1.5 +/- 0.37 microU/islet/min, P less than 0.005). Insulin release was related directly to islet size and protein content. Small islets from lean and obese animals produced less insulin per islet than large islets (P less than 0.005). In terms of islet volume, however, large islets were inefficient insulin releasers as compared to small islets (P less than 0.005). Stimulation with Br-cAMP released glucagon from islets of lean but not from large islets of obese animals (peak 11 +/- 3.3 vs. 4.1 +/- 0.3 pg/microgram protein per minute, P less than 0.05). Arginine produced the same effect on glucagon release (P less than 0.05) as stimulation with Br-cAMP. The observed increased insulin release rates and the blunted glucagon response are related to islet size in the pancreas of the Zucker rat.
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PMID:Correlation between morphology and function in isolated islets of the Zucker rat. 37 79

Genetically or experimentally-produced (e.g. via lesions of the hypothalamus) obese animals have several common features such as increased hepatic lipogenesis (resulting in fat infiltration) and increased hepatic lipoprotein secretion, together, with increased adipose tissue lipogenesis. These abnormalities appear to be related primarily to hyperinsulinemia as they are reversed to or toward normal when hyperinsulinemia is corrected or, conversely, as they develop concomitantly with hyperinsulinemia. In the liver (ob/ob mice), another defect can be demonstrated, i.e. a decreased hepatic insulin clearance. This defect is also related to hyperinsulinemia and is markedly reduced upon normalizing hyperinsulinemia of obese mice. Hyperinsulinemia may thus be a key feature of the obesity syndromes, and bring about most of the abnormalities noted, including the subsequent state of insulin resistance known to exist in obese animals. The etiology of hyperinsulinemia of genetically obese animals is still unknown. Among the possible mechanisms one should cite possible primary dysfunction of the pancreas, possible primary dysregulation, by the hypothalamus, of overall endocrine pancreas activity.
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PMID:Animal obesities. 38 57

Based on the consideration that insulin does not act directly on metabolic processes but affects membrane carriers and key-enzymes that regulate metabolic pathways, determination of insulin responsiveness of the various key-enzymes is suggested as a very appropriate method for studying insulin resistance. Insulin resistance, as it occurs in obese or obese-diabetic humans and animals, is most often associated with hyperinsulinemia, and is characterized not only by increased activity of key-enzymes of pathways known to be stimulated by insulin (glycolysis, lipogenesis), with the possible exception of glycogen synthesis, but also by a trend towards increased activity of key-enzymes of 'catabolic pathways', normally depressed by insulin. In the adipose tissue there is a normal-to-enhanced basal lipolysis, which in man would result from the prevalence of the active over the inactive form of triacylglycerol lipase. In muscle, the increased amino-acid release that can be inferred from the elevated blood level of both alanine and branched-chain amino acids suggests an enhanced proteolysis. In liver, there is an elevation in the activity of the key gluconeogenic enzymes, which forms the basis of the augmented gluconeogenesis. In both muscle and liver, phosphorylase is also elevated with no change in glycogen synthase. Therefore, insulin resistance seems to consist of the failure of insulin to depress the key-enzymes of catabolic pathways. Possible resistance of glycogen synthetase, which might account for decreased glucose utilization in muscle, may be due to the opposing effects of the phosphorylation process on glycogen synthetase and phosphorylase, implying that activation of phosphorylase (which occurs in obesity) entails inhibition of the synthetase. The fact that insulin insensitivity concerns only the 'catabolic' but not most 'anabolic' pathways makes it unlikely that the unresponsiveness is due to a reduction in insulin receptors or increase in insulin degradation. Since resistance to insulin is shown by enzymes regulated by such different mechanisms as induction-repression (gluconeogenic enzymes), covalent modifications (lipase, phosphorylase), and changes in lysosome stability (lysosomal proteases responsible for proteolysis, a single basic mechanism for explaining insulin insensitivity cannot be envisaged at present.
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PMID:Insulin resistance in obesity: a critical analysis at enzyme level. A review. 39 47

We have demonstrated how in psoriasis, irrespective of any diabetic family history, there exists a state of hyperinsulinism with a decreased resistance to insulin, which is aggravated by obesity. Since reviewing the latest studies concerning diabetes at the receptor level, we have carried out a comparative study dealing with insulin receptors in lymphocytes in homogeneous groups of normal, obese, and psoriatics of normal weight and overweight. We have also made a comparison regarding the behaviour of the receptors in these various metabolic states.
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PMID:Insulin receptors in psoriasis. 39 47

We have earlier demonstrated that in psoriasis there exists a reduced tolerance to carbohydrates in association with hyperinsulinism. To pursue this problem further, we felt it worthwhile to deal with the results of the oral glucose tolerance test performed on 78 subjects (divided into homogenous groups of normal, obese and psoriatic groups, both with and without diabetic genetic history and obesity) with determinations of both blood glucose and blood insulin levels. We have calculated the insulinogenic indexes by using the techniques elaborated by various authors (I/G, delta I/delta G, AI/AG) and we have then carried out a statistical evaluation both of these indexes and of the ratio between the various indexes employing not only the usual techniques but also that of correlation and simple and multiple regression. We have done this in order to evaluate which of these indexes is better suited to demonstrate the physiopathological mechanism concerning the relationship between insulin hypersecretion and reduced carbohydrate tolerance in the various pathological conditions which we have dealt with.
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PMID:Insulinogenic indexes in psoriasis. 39 48


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