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

Recent studies have led to an enhanced understanding of cellular alterations that may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM). The insulin receptor links insulin binding at the cell surface to intracellular activation of insulin's effects. This transducer function involves the tyrosine kinase property of the beta-subunit of the receptor. It was found that adipocytes from subjects with NIDDM had a 50 to 80 percent reduction in insulin-stimulated receptor kinase activity compared with their non-diabetic counterparts. This defect was relatively specific for the diabetic state since no decrease was observed in insulin-resistant non-diabetic obese subjects. The reduction in kinase activity was accounted for by changes in the ratio of two pools of receptors, both of which bind insulin but only one of which is capable of tyrosine autophosphorylation and subsequent kinase activation; 43 percent of the receptors from non-diabetic subjects were capable of autophosphorylation compared with only 14 percent in the NIDDM group. A major component of cellular insulin resistance in NIDDM involves the glucose transport system. Exposure of cells to insulin normally results in enhanced glucose transport mediated by translocation of glucose transporters from a low-density microsomal intracellular pool to the plasma membrane. It was found that cells from NIDDM subjects had a marked depletion of glucose transporters in both plasma membranes and low-density microsomes, relative to obese non-diabetic control participants. Obese non-diabetic persons had a normal number of plasma membrane transporters but a reduced number of low-density microsome transporters in the basal state compared with lean control volunteers; insulin induced the translocation of relatively fewer transporters from the low-density microsome to the plasma membrane in the obese subgroups. In addition to the diminished number of glucose transporters, cells from both NIDDM and obese subjects had impaired functional activity of glucose carriers since decreased whole-cell glucose transport rates could not be entirely explained by the magnitude of the decrement in the number of plasma membrane transporters. Thus, impaired glucose transport is due to both a numerical and functional defect in glucose transporters. The cellular content of high-density microsomal transporters was the same in lean and obese control volunteers and NIDDM subjects, suggesting that transporter synthesis is normal and that cellular depletion results from increased protein turnover once transporters leave the high-density microsomal subfraction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cellular mechanisms of insulin resistance in non-insulin-dependent (type II) diabetes. 305 97

To clarify whether hyperinsulinemia accelerates sympathetic nervous system (SNS) activity, norepinephrine (NE) turnover, a reliable indicator of SNS activity, was measured in the interscapular brown adipose tissue (IBAT) and heart of hyperinsulinemic yellow KK and normoinsulinemic C57BL control mice at 12 weeks of age. The yellow KK mice were more obese and had higher levels of plasma glucose (about 2.3 times) and of plasma insulin (about 24 times) than did the control mice. In IBAT, the rate of NE turnover following blockade of NE synthesis with alpha-methyl-p-tyrosine (alpha-MPT) was significantly slower in yellow KK mice than in C57BL mice, although in heart, no significant difference between both groups was observed in NE turnover. These results suggest that hyperinsulinemia dose not always increase NE turnover, and furthermore that the reduced NE turnover in IBAT of yellow KK mice may be one of the important factors in the development of obesity of this animal, as it is recognized that brown adipose tissue is a main effector of diet-induced thermogenesis and its defect or absence would predispose to obesity.
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PMID:Hyperinsulinemic yellow KK mice and norepinephrine turnover. 367 50

Norepinephrine (NE) turnover, which is a reliable indicator of sympathetic nervous system (SNS) activity, was measured in the interscapular brown adipose tissue (IBAT), heart, and pancreas of ovariectomized (OVX), sham-operated rats receiving injections of estradiol benzoate (EB). Ovariectomized rats (OVX rats) ate much more than controls and became obese, whereas the administration of EB to obese OVX rats decreased their food intake to the level below that of sham-operated animals and body weight to the level of sham controls. The results from studies using the inhibition of NE biosynthesis with alpha-methyl-p-tyrosine or radiolabeled NE to measure NE turnover significantly demonstrated reductions in SNS activity in IBAT of OVX rats than in sham controls, whereas the injections of EB to OVX rats significantly restored the decrease of NE turnover in IBAT. NE turnover in heart and pancreas were similar in these three groups. It is suggested that reduced NE turnover in IBAT may be a major factor in the development of obesity after ovariectomy (OVX).
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PMID:Reduced norepinephrine turnover in interscapular brown adipose tissue of obese rats after ovariectomy. 379 94

Obese and lean Zucker rats were made diabetic by intracardiac injections of alloxan (65-72 mg/kg body weight) and then given daily injections of protamine zinc insulin [1.25 U/(100 g/d)] for 6, 9 and 12 d. Body weight, food intake, plasma glucose and immunoreactive insulin concentrations were not different for lean and obese diabetic rats of similar ages. Rates of increase in carcass protein, mixed muscle protein and myofibrillar protein were less in obese than in lean rats. However, rates of increase for the sarcoplasmic fraction were not different. Fractional rates of synthesis of total muscle protein and myofibrillar protein, as determined by continuous intravenous infusion of [14C]tyrosine, were comparable in the two genotypes. Fractional rate of myofibrillar protein degradation, as determined by urinary 3-methylhistidine excretion, was higher in obese than in lean rats. Differences in calculated absolute rates between genotypes did not parallel differences in the fractional rates, due mainly to a smaller protein mass in obese rats. As a consequence, absolute synthetic rates were lower in obese rats, while absolute degradation rates were similar in the two genotypes. In contrast, rates of liver protein synthesis were similar in obese and lean rats, whether expressed as fractional or absolute rates. These results indicate that decreased protein deposition in the obese animal is a consequence of both an absolute decrease in protein synthesis in muscle as well as a disproportionately elevated protein degradation in muscle. Hyperinsulinemia normally seen in obese rats may be an adaptive response to minimize the impaired balance between protein synthesis and degradation.
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PMID:Protein turnover in insulin-treated, alloxan-diabetic lean and obese Zucker rats. 389 2

Identification of the fundamental polypeptide difference between yellow (A(y)/-, A(vy)/-) and non-yellow mice is important for biomedical research because of the influence of the yellow genotype on normal and neoplastic growth and obesity. The complexity of the "yellow mouse syndrome" makes attainment of this objective dependent on the separation of those pleiotropic enzyme differences which are secondary, and depend on the background genome, from those which are primary, and depend primarily on the agouti locus genotype.-Four of nine hepatic enzyme activities assayed simultaneously differed between eight-week-old yellow (A(y)/-, A(vy)/-) and non-yellow (A/-, a/a) male inbred and F(1) hybrid mice. Among these four, only cytoplasmic malic enzyme activity was elevated in all yellow mice, as compared with the non-yellow sibs, regardless of background genome. Glucokinase, serine dehydratase, and tyrosine alpha-ketoglutarate transaminase activities were also changed in yellow mice, but these alterations depended on the background genome.-The ratio of malic enzyme activity to citrate-cleavage enzyme activity, possibly related to the altered fat metabolism of yellow mice, was influenced by background genome as well as by the yellow genotype.--Significant deviations of enzyme activities from mid-parent values among F(1) hybrids were associated with particular background genomes; the number of such deviations was larger among yellow mice than among non-yellows and this difference was greater among C3H F(1) hybrids than among C57BL/6 F(1) hybrids.
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PMID:Influence of background genome on enzymatic characteristics of yellow (A v -, A vy -) mice. 440 52

The insulin-like activity of the pituitary pars-intermedia insulin secretagogue beta-cell-tropin, ACTH22-39, has been studied on rat adipocytes. The peptide was prepared by tryptic digestion of synthetic human CLIP, ACTH18-39. beta-Cell-tropin stimulated the incorporation of 3H2O into total lipids. The 50% maximal activity concentration was 5 X 10(-2) ng/ml-1 about 2.5 X 10(-11) M. Iodination of tyrosine, the penultimate amino-acid of the N-terminal, eliminated lipogenic activity, and acetylation of the N-terminal valine reduced activity. ACTH and CLIP (ACTH18-39) had no lipogenic action on the adipocyte system studied. beta-Cell-tropin stimulated the oxidation of glucose and the conversion of glucose into saponified fatty acids and glyceride glycerol. The influence of beta-cell-tropin and insulin on the incorporation of glucose into total lipids, saponified fatty acids and glyceride glycerol was not additive. The results suggest that beta-cell-tropin is either a potent lipogenic hormone, stimulating the conversion of glucose into lipids or that it activates endogenous insulin. The biological activity is associated with the N-terminal amino-acids of the peptide. The possible significance of beta-cell-tropin in obesity is discussed.
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PMID:The insulin-like action of beta-cell-tropin on glucose and lipid metabolism in adipocytes. 609 18

Sprague-Dawley rats developed diet-induced obesity (DIO) after 3 mo on a high-fat, high-sucrose diet (DIO diet), with associated increases in total body and interscapular brown adipose tissue (IBAT) lipid content. After 7 days on the DIO diet, rats had increased levels of tyrosine hydroxylase (TH; 34%), norepinephrine (NE; 34%), and NE turnover (94%; estimated by alpha-methyl-p-tyrosine inhibition of TH) in their IBAT compared with chow-fed controls. After 3 mo on the DIO diet, NE levels and/or turnover were reduced by 27-50% in aortas, hearts, and pancreata in obese rats. While IBAT NE turnover was normal, TH inhibition failed to increase the lipid content of IBAT in obese rats as it did in controls, suggesting a postsynaptic defect in basal NE-stimulated lipolysis in this thermogenically active tissue. When obese rats were switched from the DIO diet to rat chow for 3 days, NE levels remained depressed in their hearts (25%) and aortas (14%) but were increased by 36-45% in IBAT, pancreata, and white adipose tissue. NE turnover rates and/or constants were increased by 37-110% in hearts, aortas, pancreata, and IBAT of these obese rats while there were increased IBAT TH (20%) and dopamine-beta-hydroxylase (87%) activities compared with chow-fed controls. Therefore, sympathetic activity varied markedly as a function of both dietary composition and relative body weight during the development of DIO.
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PMID:Altered sympathetic activity during development of diet-induced obesity in rat. 613 10

The effects of insulin and insulin-like growth factor I (IFG-I) on protein synthesis were compared in muscle isolated from lean and goldthioglucose (GTG)-obese mice. Two types of skeletal muscles, the red soleus and the white extensor digitorum longus (EDL) muscles, were studied. In muscles from lean mice, 6.7 nM insulin and 50 nM IGF-I caused a similar maximal stimulation of tyrosine incorporation in total proteins (40% increase). However, the potency of IGF-I was only 5-10% that of insulin both in soleus and in EDL muscles (EC50 approximately equal to 6 nM for IGF-I and 0.5 nM for insulin). Basal rate of protein synthesis was identical in muscles from GTG-obese and lean mice. Similarly, a comparable increase in the rate of protein synthesis was obtained using maximally effective concentrations of insulin and IGF-I in both lean and GTG-obese animals. SDS-polyacrylamide gel electrophoresis analysis of proteins labeled with 35S-methionine confirmed that, in muscles from lean and GTG-obese animals, insulin and IGF-I increased overall protein synthesis in a similar manner. These results suggest that the protein synthesis machinery is not impaired in GTG-induced obesity, which is therefore not associated with resistance to insulin for its effect on protein metabolism.
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PMID:Insulin and insulin-like growth factor I. Effects on protein synthesis in isolated muscles from lean and goldthioglucose-obese mice. 640 79

The disappearance of norepinephrine from the heart, interscapular brown adipose tissue (BAT), and pancreas has been examined in mice with monosodium glutamate (MSG)-induced obesity and in untreated controls. MSG-treated mice became obese in the absence of increased food intake and their core temperature was significantly lower compared to control mice. The rate of norepinephrine turnover following blockade of norepinephrine synthesis with alpha-methyl-para-tyrosine was significantly slower in heart and interscapular BAT of these mice than in untreated controls, but MSG had no effect on the pancreas. It is suggested that reduced norepinephrine turnover may be a major factor in the development of obesity after neonatal administration of MSG.
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PMID:Reduced norepinephrine turnover in mice with monosodium glutamate-induced obesity. 649 48

The effect of obesity and tyrosine (tyr) supplements on catecholamine metabolism in 12 normal weight and nine obese adult women was studied. Protein intake was maintained at 1.4 g protein/kg fat-free mass daily for 4 days with tyr added (0.26 g/kg fat-free mass) to the liquid diet on the last 2 days. In the 12 normal subjects, but not the obese, base-line urinary excretion of the norepinephrine metabolite, 3-methoxy-4-hydroxy phenylethyleneglycol was related to body fat whereas excretion of the norepinephrine metabolite vanilmandelic acid was related to fat-free mass and to total energy intake. Normal subjects responded to tyr with elevations in plasma tyr/neutral amino acid, plasma 3-methoxy-4-hydroxy phenylethyleneglycol, urinary vanilmandelic acid, and homovanillic acid, a dopamine metabolite, but not the norepinephrine metabolite, dihydroxy phenylethyleneglycol. The obese showed no increase in plasma or urinary 3-methoxy-4-hydroxy phenylethyleneglycol during tyr supplementation, although vanilmandelic acid and homovanillic acid increased. We conclude that urinary catecholamine metabolite production is related to body composition and to tyr intake in normal weight women. These relationships however, are altered in the obese, suggesting an association of obesity with abnormal catecholamine metabolism.
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PMID:Obesity and precursor availability affect urinary catecholamine metabolite production in women. 661 10


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