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

We tested the hypothesis that endothelium-dependent vasodilatation is a determinant of insulin resistance of skeletal muscle glucose uptake in human obesity. Eight obese (age 26+/-1 yr, body mass index 37+/-1 kg/m2) and seven nonobese males (25+/-2 yr, 23+/-1 kg/m2) received an infusion of bradykinin into the femoral artery of one leg under intravenously maintained normoglycemic hyperinsulinemic conditions. Blood flow was measured simultaneously in the bradykinin and insulin- and the insulin-infused leg before and during hyperinsulinemia using [15O]-labeled water ([15O]H2O) and positron emission tomography (PET). Glucose uptake was quantitated immediately thereafter in both legs using [18F]- fluoro-deoxy-glucose ([18F]FDG) and PET. Whole body insulin-stimulated glucose uptake was lower in the obese (507+/-47 mumol/m2 . min) than the nonobese (1205+/-97 micromol/m2 . min, P < 0.001) subjects. Muscle glucose uptake in the insulin-infused leg was 66% lower in the obese (19+/-4 micromol/kg muscle . min) than in the nonobese (56+/-9 micromol/kg muscle . min, P < 0.005) subjects. Bradykinin increased blood flow during hyperinsulinemia in the obese subjects by 75% from 16+/-1 to 28+/-4 ml/kg muscle . min (P < 0.05), and in the normal subjects by 65% from 23+/-3 to 38+/-9 ml/kg muscle . min (P < 0.05). However, this flow increase required twice as much bradykinin in the obese (51+/-3 microg over 100 min) than in the normal (25+/-1 mug, P < 0.001) subjects. In the obese subjects, blood flow in the bradykinin and insulin-infused leg (28+/-4 ml/kg muscle . min) was comparable to that in the insulin-infused leg in the normal subjects during hyperinsulinemia (24+/-5 ml/kg muscle . min). Despite this, insulin-stimulated glucose uptake remained unchanged in the bradykinin and insulin-infused leg (18+/-4 mumol/kg . min) compared with the insulin-infused leg (19+/-4 micromol/kg muscle . min) in the obese subjects. Insulin-stimulated glucose uptake also was unaffected by bradykinin in the normal subjects (58+/-10 vs. 56+/-9 micromol/kg . min, bradykinin and insulin versus insulin leg). These data demonstrate that obesity is characterized by two distinct defects in skeletal muscle: insulin resistance of cellular glucose extraction and impaired endothelium-dependent vasodilatation. Since a 75% increase in blood flow does not alter glucose uptake, insulin resistance in obesity cannot be overcome by normalizing muscle blood flow.
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PMID:Insulin resistance of glucose uptake in skeletal muscle cannot be ameliorated by enhancing endothelium-dependent blood flow in obesity. 948 87

It has been postulated that glucose transport is the principal site of skeletal muscle insulin resistance in obesity and type 2 diabetes, though a distribution of control between glucose transport and phosphorylation has also been proposed. The current study examined whether the respective contributions of transport and phosphorylation to insulin resistance are modulated across a dose range of insulin stimulation. Rate constants for transport and phosphorylation in skeletal muscle were estimated using dynamic positron emission tomography (PET) imaging of 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) during insulin infusions at three rates (0, 40, and 120 mU/m2 per min) in lean glucose-tolerant, obese glucose-tolerant, and obese type 2 diabetic subjects. Parallel studies of arteriovenous fractional extraction across the leg of [18F]FDG and [2-3H] glucose were performed to measure the "lumped constant" (LC) (i.e., the analog effect) for [18F]FDG to determine whether this value is affected by insulin dose or insulin resistance. The value of the LC was similar across insulin doses and groups. Leg glucose uptake (LGU) also provided a measure of skeletal muscle glucose metabolism independent of PET. [18F]FDG uptake determined by PET imaging strongly correlated with LGU across groups and across insulin doses (r = 0.81, P < 0.001). Likewise, LGU correlated with PET parameters of glucose transport (r = 0.67, P < 0.001) and glucose phosphorylation (r = 0.86, P < 0.001). Glucose transport increased in response to insulin in the lean and obese groups (P < 0.05), but did not increase significantly in the type 2 diabetic group. A dose-responsive pattern of stimulation of glucose phosphorylation was observed in all groups of subjects (P < 0.05); however, glucose phosphorylation was lower in both the obese and type 2 diabetic groups compared with the lean group at the moderate insulin dose (P < 0.05). These findings indicate an important interaction between transport and phosphorylation in the insulin resistance of obesity and type 2 diabetes.
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PMID:Interactions of impaired glucose transport and phosphorylation in skeletal muscle insulin resistance: a dose-response assessment using positron emission tomography. 1152 73

A controversial area in understanding the contribution of obesity to skeletal muscle insulin resistance is the distribution of control of glucose metabolism across proximal steps of glucose delivery, trans-membrane transport, and intracellular trapping via phosphorylation. Dynamic positron emission tomography (PET) imaging of skeletal muscle [(18)F]2-deoxy-2-D-glucose ((18)F-FDG) uptake provides an in vivo method for assessment of these steps in humans. In the current study we have examined the application of a four-compartment skeletal muscle-specific model for assessment of (18)F-FDG metabolism that takes interstitial (18)F-FDG kinetics into account and compared this to the classic three-compartment model in lean and obese volunteers. We assessed the effects of insulin infusions at three rates (0, 40, and 120 mU/m(2).min). In comparison with the classic model, the skeletal muscle-specific model reveals more clearly definable effects of insulin on transmembrane glucose transport and an impairment of this response in obesity. Compared with the classic model for assessment of (18)F-FDG metabolism, both the skeletal muscle-specific and the classic model indicate that, with respect to distribution of control, glucose phosphorylation has an important effect at low to moderate levels of insulin stimulation in both lean and obese subjects.
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PMID:Glucose transport and phosphorylation in skeletal muscle in obesity: insight from a muscle-specific positron emission tomography model. 1262 18

Obesity is a major factor central to the development of insulin resistance and type 2 diabetes. The identification and characterization of genes involved in regulation of adiposity, insulin sensitivity, and glucose uptake are key to the design and development of new drug therapies for this disease. In this study, we show that the polarity kinase Par-1b/MARK2 is required for regulating glucose metabolism in vivo. Mice null for Par-1b were lean, insulin hypersensitive, resistant to high-fat diet-induced weight gain, and hypermetabolic. (18)F-FDG microPET and hyperinsulinemic-euglycemic clamp analyses demonstrated increased glucose uptake into white and brown adipose tissue, but not into skeletal muscle of Par-1b null mice relative to wild-type controls. Taken together, these data indicate that Par-1b is a regulator of glucose metabolism and adiposity in the whole animal and may be a valuable drug target for the treatment of both type 2 diabetes and obesity.
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PMID:Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo. 1737 92

The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.
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PMID:Unexpected evidence for active brown adipose tissue in adult humans. 1791 51

Currently there is tremendous interest in obesity and its harmful donsequences. Height, weight and body mass index (BMI) along with waist girth are routinely used parameters. One snag in the interpretation of BMI >25 as a measure of obesity is the assumption that the increase is mainly due to fat. This review emphasizes the importance of assessing the muscle component of BMI (by simple somatoscopy or somatotyping). 75 percent of Indian T2DM patients have a normal or low BMI, only 25 percent have BMI >25, wherein muscle mass also contributes as well as fat. Hyperinsulinemia is anabolic to both fat and muscle. Since skeletal muscle is a primary site of insulin resistance, greater the muscle mass, greater the importance of physical exercise to overcome the insulin resistance and greater the importance of dietary supplement of n3-PUFA to optimize the phospholipid composition of the muscle membrane (increasing membrane fluidity and thereby permitting longer residence of GLUT-4 in the plasma membrane). I propose three testable hypotheses: (1) Brown fat (FDG-PET imaging) and UCP2 and UCP3 expression in muscle are positively correlated with ectomorphy and mesomorphy, and negatively correlated with endomorphy and obesity. BAT is absent in obese people. (2) Indian T2DM patients with normal or low BMI have increased UCP2 and UCP3 expession in their muscle, as well as increased high molecular weight adiponectin which promote fatty acid oxidation and prevent obesity. (3) Indian T2DM with BMI >25 and obesity have dysfunction of UCP2 and UCP3. They have high leptin with leptin resistance (induced by hyperinsulinemia) and low adiponectin. There is inverse relationship between adipose mass and adiponectin production.
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PMID:Fat and muscle component of body mass index (BMI): relation with hyperinsulinemia. 1759 32

Carotid atherosclerosis is a leading cause of cerebrovascular events. The control of cardiovascular risk factors, i.e. tobacco smoking, alcohol abuse, hypertension, dyslipidemia, diabetes and obesity proved to reduce number of fatal and non-fatal strokes but failed to prevent important number of them. Screening for biomarkers in individuals at high risk of symptomatic vascular disease helped to identify some of them. However, as disease is by its nature multifocal, global testing for biomarkers may have limited practical application. New imaging techniques, including direct visualization of artery metabolism, by 18-FDG-PET, has brought new tools to study local atherosclerosis progression and individual plaque metabolic activity. Advances in molecular biology helped to identify inflammatory genes and its strong link to angiogenesis. The later, is thought to play a key role in the transformation to unstable plaque. Studies of the complex role that plays angiogenesis in plaque development will help in future to design effective therapies addressed at the individual cell level. The purpose of the review is to bring new insights into complicated pathophysiology of carotid atherosclerosis.
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PMID:Angiogenesis and inflammation in carotid atherosclerosis. 1850 73

Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI>40 kg/m(2)) and compared it to that in twelve non-obese controls. PET was used with [(11)C]raclopride to assess D2 receptors and with [(18)F]FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food.
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PMID:Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. 1859 72

Although impaired inhibitory control is linked to a broad spectrum of health problems, including obesity, the brain mechanism(s) underlying voluntary control of hunger are not well understood. We assessed the brain circuits involved in voluntary inhibition of hunger during food stimulation in 23 fasted men and women using PET and 2-deoxy-2[(18)F]fluoro-D-glucose ((18)FDG). In men, but not in women, food stimulation with inhibition significantly decreased activation in amygdala, hippocampus, insula, orbitofrontal cortex, and striatum, which are regions involved in emotional regulation, conditioning, and motivation. The suppressed activation of the orbitofrontal cortex with inhibition in men was associated with decreases in self-reports of hunger, which corroborates the involvement of this region in processing the conscious awareness of the drive to eat. This finding suggests a mechanism by which cognitive inhibition decreases the desire for food and implicates lower ability to suppress hunger in women as a contributing factor to gender differences in obesity.
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PMID:Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation. 1932 32

Persistent hyperinsulinemic hypoglycemia (PHH) is caused by solitary benign insulinoma or hyperplasia of pancreatic beta cells. In infants, PHH is caused by functionally defective hyperplastic beta cells, which are either diffusely or focally distributed in the pancreas. In adults, insulinoma is the most common cause of PHH, but recently, an increasing number of beta-cell hyperplasias has been reported among adults. The cause of adult beta-cell hyperplasia is not known. Whether the increased use of bariatric surgery in the treatment of severe obesity plays a role here is under investigation. Accurate localization of disease focus in both insulinoma and focal beta-cell hyperplasia provides an important support for surgery, especially as the use of laparoscopic surgery has increased. Conventional imaging of these challenging pancreatic lesions has evolved during recent years, but current imaging methods still lack sufficient sensitivity or are invasive. In most pancreatic NETs, the usefulness of positron emission tomography (PET) with fluorine-labeled fluorodeoxyglucose ([(18)F]FDG) for lesion detection is limited because of the low glucose turnover of these tumors. Based on the capacity of pancreatic beta cells to take up and decarboxylate amine precursors, several investigators have studied patients with pancreatic NETs using aminoacid precursors, such as [(18)F]dihydroxyphenylalanine (DOPA) and [(11)C]hydroxytryptophan (5-HTP), in an attempt to increase the sensitivity of PET scanning. Another characteristic of NETs is the expression of somatostatin receptors, and thus encouraging studies with somatostatin receptor imaging with [(18)Ga]-labeled somatostatin analogs have emerged as a new interesting imaging tool for the diagnosis of pancreatic NETs. This article provides an overview of our experiences and the current literature on PET imaging in patients with PHH caused by insulinoma or beta-cell hyperplasia.
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PMID:Clinical PET imaging of insulinoma and beta-cell hyperplasia. 2014 60


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