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

The status of insulin-receptor interactions in a variety of insulin-resistant states is reviewed. Utilizing large adipocytes from adult rats and small fat cells from young rats, we have conducted a series of in vitro experiments in an attempt to determine the cellular alteration(s) responsible for the insulin resistance associated with obesity. Stimulation of glucose oxidation by insulin is reduced in large cells. Studies using a mimicker of insulin action, spermine, as well as measurements of 125I-insulin binding to large and small cells indicate that receptor number and affinity are not responsible for hormone resistance. Furthermore, when rapid and direct measurements of sugar uptake were made, insulin stimulation was virtually identical in both cell types. These findings indicate that large adipocytes have an efficient insulin-responsive D-glucose transport system and suggest that the apparent hormone resistance may be due to alterations in intracellular glucose metabolism. It has been proposed that altered insulin-receptor interaction underlies the insulin resistance of human obesity. We have investigated this particular aspect of insulin action by 125I-insulin binding studies. Similar numbers of insulin receptors per cell and affinity for insulin were observed in adipocytes obtained from normal weight subjects and morbidly obese patients. Thus, the initial step in insulin action is unaltered in human obesity.
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PMID:Relation of insulin receptors to insulin resistance. 16 83

The effect of a new complex oligosaccharide exhibiting potent inhibitory action on alpha-glucoside hydrolases on intestinal absorption of sucrose in man was tested by constant in vivo perfusion of the jejunum. At concentrations of 4.65 or 15.5 X 10(-6)M the alpha-glucosidehydrolase inhibitor (alpha-GHI) markedly inhibited absorption of glucose from sucrose and absorption of sodium and water. Oral administration of the alpha-GHI resulted as well in depression of solute, sodium, and water absorption. This new compound can serve as an interesting tool to induce carbohydrate malabsorption by inhibition of final digestion and may possibly be of beneficial therapeutic effect in dietary control of diabetes or obesity.
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PMID:Effect of alpha-glucosidehydrolase inhibition and intestinal absorption of sucrose, water, and sodium in man. 38 40

A dose-response relationship for the effects of 2-deoxy-D-glucose (2-DG) (0-400 mg/kg) on food intake was established in normal and obese ventromedial hypothalamic lesioned rats. In normal animals the lowest dose that produced a statistically signififant increase over baseline food intake was 100 mg/kg 2-DG. Larger doses produced a progressively greater effect. Most of the increase in food intake occurred during the first hour after the injection of 2-DG, the latency of the first feeding bout being shorter for higher doses of the compound. Obese VMH rats significantly increased their 4-hr food intake after 150, 200, and 250, and 400 mg/kg 2-DG, but the increase in feeding was delayed compared to control animals. During the first hour after the injection, the food intake of obese rats was unaffected by doses of 2-DG up to 250 mg/kg, and inhibited by higher doses (300 and 400 mg/kg). The effects of VMH lesions on 2-DG-induced eating are attributed to the elimination of afferents from peripheral glucoreceptors.
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PMID:Delayed response to 2-deoxy-D-glucose in hypothalamic obese rats. 65 34

The impact of hyperinsulinemia on the establishment of insulin resistance was investigated. This was done by treating normal rats with insulin for 3-4 days via osmotic minipumps, and by comparing them with saline-treated controls. Hyperinsulinemia produced by prior insulin treatment (i.e. prior insulinization of the normal rats) resulted in a well tolerated hypoglycemia, increased food intake and body weight gain. Euglycemic-hyperinsulinemic clamps were carried out at the end of the insulinization to assess the acute effects of insulin in control and insulinized rats. It was found that prior insulinization of normal rats resulted in increases in total insulin-stimulated glucose utilization and hepatic lipogenesis, while hepatic glucose production (HGP) was normally suppressed by the hormone. Glucose utilization index by individual tissues was then measured (labelled 2-deoxy-D-glucose method). Prior insulinization of normal rats resulted in increased insulin-stimulated glucose utilization index of white adipose tissue, accompanied by increased insulin-stimulated de novo lipogenesis and glycogen synthesis. In contrast, prior insulinization of normal rats resulted in a decreased insulin-stimulated glucose utilization index of most muscles studied. The decreased insulin-stimulated muscle glucose utilization index brought about by prior insulinization persisted in adrenomedullectomized or propranolol-treated rats, ruling out a role of catecholamines in the effects observed. It is concluded that hyperinsulinemia is a pathological driving force in producing both incipient obesity by overstimulating white adipose tissue and liver metabolic activity, and concomitantly producing incipient muscle insulin resistance.
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PMID:Hyperinsulinemia and its impact on obesity and insulin resistance. 133 81

It is not known whether hyperinsulinemia of the genetically obese fa/fa rat occurs before insulin resistance and abnormal glucose handling or vice versa. Therefore, it was decided to study, as a function of age, the evolution of the insulin-stimulated glucose uptake measuring the in vitro uptake of its analog, 2-deoxy-D-glucose (2DG), by diaphragm. The expression of the insulin-sensitive glucose transporter (GLUT 4) mRNA and protein were also investigated in muscles. The maximum increase over baseline in 2DG uptake in response to increasing insulin concentrations in the medium was upward shifted in diaphragm from preweaned 21-day-old preobese rats relative to that in lean controls (increased responsiveness). By 31 days of age the maximum increase over baseline diaphragm 2DG uptake in response to insulin was similar in young lean and obese rats. At 70 days of age, the 2DG uptake muscle dose response to insulin was significantly downward shifted, i.e. clearly insulin resistant (decreased responsiveness). Muscle (diaphragm and extensor digitorum longus) expression of GLUT 4 mRNA and protein revealed no intergroup difference at any of the ages studied. Hyperinsulinemia was moderate in preobese animals and progressively increased with the duration of the obesity syndrome. Based on the observation that diaphragm glucose uptake of 21-day-old preobese rats was overresponsive to insulin, normoinsulin responsive at 31 days, and insulin resistant at a later time, it is concluded that muscle insulin resistance is not a primary etiological defect, but must be secondary to other pathological alterations, the nature of which remains to be elucidated.
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PMID:Muscle insulin resistance may not be a primary etiological factor in the genetically obese fa/fa rat. 153 6

Age-related cataract is a condition characterized by multiple mechanisms and multiple risk factors. The mechanisms that bring about a loss in transparency include oxidation, osmotic stress, and chemical adduct formation. Risk factors for cataract include diabetes, radiation (ultraviolet B, x-ray), certain pharmaceutical substances, certain nutritional states, and possibly acute episodes of dehydration. Interaction occurs between and among mechanistic factors and risk factors. Thus nutrition must be considered as one part of a tapestry of intertwined events and responses. Certain experimental models for nutritional cataract have been useful for study of the cataractogenic process but are probably not important factors in the human disease. Little current evidence supports significant roles in human senile cataract for imbalances of tryptophan or other amino acids, deficiencies of calcium or selenium, or excessive intake of selenium. Overconsumption of galactose is likely to be hazardous only in subjects with genetic inability to metabolize this sugar. Vitamins with antioxidant potential (riboflavin, vitamin E, vitamin C, carotenoids) deserve further research scrutiny to ascertain their significance in cataract etiology. Excessive caloric intake needs to receive added emphasis as a factor contributing to cataract. Diabetes increases the likelihood of cataract three- to four-fold. Obesity, defined as more than 20% overweight, is considered a major risk factor for non-insulin-dependent, or type II, diabetes (69, 73). Weight control can be recommended as a prudent, safe, economic, and effective means of lowering risk probability for diabetes and the associated complication of cataract.
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PMID:Nutritional factors in cataract. 220 Apr 64

beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D-glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta-lipotropin.
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PMID:Processing of the lipid-mobilizing peptide beta-lipotropin in rabbit adipose tissue. 221 32

Soskin, in his 1946 textbook, stated that insulin may be regarded as the dominant instrument in the symphony of endocrine action that results in normal carbohydrate metabolism. After almost half a century, great progress in the medical field has revealed that insulin plays more than even he described. Some aspects of important actions of insulin in our field as investigated in our laboratory are summarized below. 1. Role of insulin in reproductive endocrinology. (1) Correlation of insulin and testosterone in normal young women and patients with polycystic ovary syndrome (PCO). The sum of serum insulin values during 75g OGTT and serum testosterone values were positively correlated in normal women and patients with PCO. Glucose transport activities in isolated adipocytes from a typical PCO patient were decreased, but insulin binding activities were not, which indicates that insulin resistance in this patients is due to some post-receptor defects. (2) Insulin may be a risk factor of endometrial carcinoma. It is well-recognized that several diseases associate with hyperinsulinemia, such as obesity, PCO, diabetes mellitus, and hypertension are risk factors for endometrial carcinoma. The sum of the insulin values during OGTT was significantly higher in patients with endometrial carcinoma than in those without. 2. Role of insulin in perinatal medicine. (1) Increase in insulin secretion during pregnancy. High serum insulin concentration during OGTT, increased secretion of urinary C-peptide, and enhanced staining of insulin in B cells by the PAP method suggest that insulin secretion is enhanced during pregnancy. (2) Insulin resistance during pregnancy. Glucose utilization rate in both pregnant and progesterone-treated rats, as assessed by a glucose clamp technique, is significantly decreased as compared to nonpregnant rats. The technique of 2-deoxyglucose injection revealed that whole body insulin resistance is due to insulin resistance in individual insulin-sensitive tissues. The activities of 3-0-methyl-D-glucose transport in isolated rat skeletal muscle and human adipocytes were found to decrease during late pregnancy, but insulin binding activities were not. These results suggest that insulin resistance during pregnancy is due to some post-receptor mechanisms. (3) Physiological meaning of insulin in fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of insulin in reproductive endocrinology and perinatal medicine]. 223 Apr 12

Approximately half the male Sprague-Dawley rats fed a high energy diet develop diet-induced obesity (DIO). The remainder are diet-resistant (DR) and do not become obese. Resistance to DIO can be predicted before exposure to high energy diets by the presence of diminished norepinephrine (NE) release to an intravenous glucose load. Here chow-fed rats were prospectively placed in DR- or DIO-prone 'diet groups' by the areas under their glucose-induced (1 g/kg, i.v.) NE curves (DR rats less than 1200 pg/ml/60 min; DIO rats greater than 4500 pg/ml/60 min). To test the central pathways involved in the response to the intake of palatable foods, rats were first trained to drink 1 ml of 50% glucose within 1 min and then were tested for local cerebral glucose utilization using uptake of [14C]2-deoxy-D-glucose ([14C]2-DG) after receiving 0.15% sodium saccharin in place of glucose to avoid altering plasma glucose levels. Controls for basal cerebral metabolism (C) received no solution. DR-prone rats increased [14C]2-DG uptake by 60-190% in autonomic areas of the medulla (nucleus tractus solitarius, area postrema, dorsal motor nucleus X) and amygdala (central nucleus) in the S versus C conditions while DIO-prone rats had high basal levels of [14C]2-DG uptake in these areas and showed no increase after S. Also, DR-prone rats had 9-25% higher [14C]2-DG uptake in the ventromedial hypothalamic nucleus than DIO rats regardless of C or S conditions. Thus, pre-existing differences in the activation of autonomic areas of the brain in response to a food-related cue may be of etiological significance in the different patterns of food intake and weight gain seen in DR- and DIO-prone rats fed a high energy diet.
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PMID:Differences in saccharin-induced cerebral glucose utilization between obesity-prone and -resistant rats. 274 18

Binding sites for [3H](+)-amphetamine in the hypothalamus may mediate the anorectic actions of amphetamine and related phenylethylamines. To investigate further the role of these sites in the central control of appetite, the binding of [3H](+)-amphetamine to the hypothalamus and brainstem was measured following food deprivation and refeeding, the onset of genetic obesity, or the administration of 2-deoxy-D-glucose. Food deprivation for 24 to 72 hours reduced the Bmax for [3H](+)-amphetamine binding in the hypothalamus and brainstem but not in other brain areas or peripheral tissues. The decrease in hypothalamic and brainstem [3H](+)-amphetamine binding observed following food deprivation was time-dependent and rapidly reversed by brief refeeding with either rat chow or a 10% glucose solution. Moreover the changes in [3H](+)-amphetamine binding were highly correlated to corresponding alterations in blood glucose concentration. Furthermore, D-glucose, but not L-glucose increases the number of hypothalamic [3H](+)-amphetamine binding sites when administered in vivo or when added to hypothalamic slices in vitro. These data suggest that the [3H](+)-amphetamine binding site in the hypothalamus and (or) brainstem may be coupled to a central "glucostat."
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PMID:Glucose regulates [3H](+)-amphetamine binding and Na+K+ ATPase activity in the hypothalamus: a proposed mechanism for the glucostatic control of feeding and satiety. 300 57


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