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

Ventromedial hypothalamic (VMH)-lesioned rats were tested 1 and 6 wk after the lesions to determine, by euglycemic-hyperinsulinemic clamps, their tissue response to insulin. One week after the lesions, total glucose metabolism was more sensitive and responsive to insulin than in age-matched controls. In the two groups, hepatic glucose production was suppressed at almost identical insulin concentrations (approximately 550 microU/ml). Six weeks after the VMH lesions, the increased insulin responsiveness of total glucose metabolism disappeared and glucose metabolism became less insulin sensitive (right, shifted dose-response curve) than that of control animals. Furthermore, hepatic glucose production of VMH-lesioned rats was now inhibited by 45% at most and at the supraphysiological insulin concentration of 16,000 microU/ml, while it was totally suppressed by 550 microU/ml of the hormone in age-matched controls. This defect was accompanied by a lack of decrease in plasma glucagon levels during the clamps carried out at maximal insulin concentration. In summary, in a first phase after VMH lesion, rats are hypersensitive and hyperresponsive to insulin; and in a later phase, when obesity is well established, VMH-lesioned rats become insulin resistant and are characterized by a decreased in vivo sensitivity and responsiveness of liver and muscles to the hormone.
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PMID:In vivo metabolic changes as studied longitudinally after ventromedial hypothalamic lesions. 352 13

Fasting and postprandial plasma concentrations of glucose, FFA, insulin, glucagon, and GH concentrations were determined in 10 nonobese and 10 obese subjects with normal glucose tolerance. Measurements were made at 0800 h (after a 14-h fast) and at hourly intervals from then until 1600 h. During this time period all individuals ate breakfast at 0800 h (20% of total daily calories) and lunch (40% of total daily calories). Although plasma glucose concentrations were similar throughout the 8-h period in the 2 groups, plasma insulin concentrations were significantly (P less than 0.001) higher in the obese individuals. However, despite the presence of hyperinsulinemia, the obese group also had higher (P less than 0.001) plasma FFA concentration throughout the day. On the other hand, both the absolute and the relative declines in plasma FFA concentration after meals were similar in the 2 groups. Since plasma glucagon and GH concentrations were similar in the 2 groups, altered production of these lipolytic hormones was not responsible for the elevated plasma FFA levels in the obese individuals. These data document the presence in obese individuals of a disassociation in their ability to maintain normal plasma glucose as opposed to plasma FFA homeostasis, and indicate that the increase in plasma FFA concentrations in obesity occurs in the presence of hyperinsulinemia and is not related to abnormalities of either glucagon or GH secretion.
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PMID:Effect of obesity on ambient plasma glucose, free fatty acid, insulin, growth hormone, and glucagon concentrations. 352 20

The ability of a serum fraction, mol wt 1000-5000, to stimulate insulin release in vitro was studied in 123 obese and normal weight children aged 0-17 yr. The sera were fractionated by serial molecular filtration after treatment with urea. Stimulation of insulin release was determined with a bioassay using isolated rat islets in perifusion. The islet-stimulating activity was found in all obese children less than the age of 10 yr and in the majority of the obese children older than 10 yr of age. In normal weight children the activity was also found in the majority of infants, but was infrequent in older children. The serum islet-stimulating activity was positively correlated with the duration and degree of obesity and with linear growth rate. The molecular structure and origin of the insulinogenic activity in the serum is still unknown. In high-performance liquid chromatography it has the same elution characteristics as the hypothalamic insulin-glucagon liberin. The present results suggest a role for the serum islet-stimulating activity in the pathogenesis of obesity.
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PMID:Insulinotropic activity in the serum of obese and nonobese infants and children. 352 64

We compared sensitivity, specificity and accuracy of selected clinical characteristics (age at diagnosis, initiation of permanent insulin therapy from diagnosis and degree of obesity) in the discrimination between diabetics with low or high fasting or post-glucagon C-peptide level in a population of 171 middle-aged insulin-treated diabetics (81 men, 90 women) living in East Finland. Individual clinical criteria were poor discriminators alone but their combinations gave high specificity for the low and high fasting and post-glucagon C-peptide classes. The specificity and the accuracy of combined criteria seemed to be somewhat higher among male than among female insulin-treated diabetics. The association between clinical characteristics and fasting or postglucagon C-peptide classes seemed to be similar.
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PMID:Clinical characteristics in the discrimination between patients with low or high C-peptide level among middle-aged insulin-treated diabetics. 358 63

We have studied fasting, postprandial and postprandial plus glucagon-stimulated plasma C-peptide levels in 149 non-insulin-dependent diabetics treated either with diet or oral drugs and in 101 non-diabetic control subjects. Diet-treated diabetics showed the highest fasting, postprandial and post-glucagon C-peptide levels in both sexes. In men, diabetics treated with oral drugs showed lower postprandial and glucagon-stimulated C-peptide levels than control subjects, while in women C-peptide levels in this group of diabetics were similar to those in control subjects. The distribution of individual plasma C-peptide levels was wide in non-insulin-dependent diabetics and control subjects and there was considerable overlapping in plasma C-peptide distribution for diabetics and control subjects. Fasting and post-glucagon plasma C-peptide levels in diabetics showed an inverse association to plasma glucose levels and a positive association to degree of obesity, but no association with the known duration of diabetes.
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PMID:Fasting, postprandial and postprandial plus glucagon-stimulated plasma C-peptide levels in non-insulin-dependent diabetics and in control subjects. 360 53

To evaluate the metabolic basis of gestational glucose intolerance (gestational diabetes), the response of normal pregnant women (N=6) and lean (N=23), and obese (N=12) gestational diabetics to the physiologic challenge of a 400-kcal mixed meal breakfast tolerance test was studied. Obese patients with gestational diabetes were more hyperglycemic than the lean gestational diabetics in both the fasting and postprandial periods. Women with gestational diabetes had a more prolonged glycemic response and a later insulin response to meal stimulation than normal control subjects. Fasting and postprandial insulin levels were higher in the obese gestational diabetes group, whereas those of lean subjects fell below the values of the control group. The percent specific binding of insulin to red blood cell receptors was lower in both gestational diabetes groups than in control subjects, with the most marked decrease in the obese group. Mean fasting plasma levels of total cholesterol and triglyceride and plasma glucagon levels during the meal tolerance test were not significantly different among the three groups. Obese gestational diabetics had significantly larger infants and placentas than lean gestational diabetics. These findings, taken together, suggest that the pathophysiology of gestational diabetes differs between obese and lean patients. Lean gestational diabetics appear to develop glucose intolerance on the basis of relative insulin deficiency in contrast to obese gestational diabetics who manifest glucose intolerance characterized by insulin resistance, hyperinsulinemia, and decreased insulin binding to red blood cell receptors.
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PMID:Demonstration of heterogeneity in gestational diabetes by a 400-kcal breakfast meal tolerance test. 388 Aug 78

Mature male Sprague-Dawley rats fed a powdered Purina Chow diet containing corn oil and condensed milk (CM) were compared to rats fed a Purina Chow diet (control). CM rats gained more weight and consumed more calories over a 73-day period than the control rats. The increased weight gain and body fat in CM rats was accompanied by increased cell number in retroperitoneal and inguinal but not epididymal fat pads while cell size was unchanged in all three pads. After obesity had developed there was an increase in insulin levels, lipolysis, hepatic fatty acid synthesis, and fatty acid oxidation. While CM rats demonstrated hyperinsulinemia and hyperglycerolemia, they maintained normal glucagon and glucose levels. They demonstrated higher rates of fatty acid synthesis in isolated hepatocytes but not in vivo, suggesting that a greater potential for fatty acid synthesis in CM rats was masked in vivo by the inhibitory action of dietary lipids. Beta-oxidation of (1-14C) palmitate in vivo and in vitro, and in vivo ketogenesis were greater in CM than in chow fed rats. These studies demonstrate that, after the development of obesity, CM rats, like genetically obese Zucker rats, are hyperinsulinemic and have elevated levels of fatty acid synthesis. However, unlike obese Zucker rats, CM rats displayed an increase in beta-oxidation. These studies suggest that increased insulin levels and hepatic fatty acid synthesis may contribute to dietary obesity (as they do to genetic obesity), whereas increased fatty acid oxidation in dietary obesity may be a compensatory response to maintain a lower body weight.
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PMID:Changes in lipid metabolism in diet-induced obesity. 388 41

We reported that significant rapid oscillations occur in basal plasma levels of insulin, glucagon, and glucose in rhesus monkeys and humans. We searched for evidence for similar spontaneous fluctuations also in plasma levels of pancreatic polypeptide (PP). Mean +/- SE basal plasma levels of PP were 236 +/- 15 pg/ml in 11 monkeys, 64 +/- 12 in nine normal-weight human subjects, and 74 +/- 10 in nine obese human subjects. 1) PP levels fluctuated with periods of 6-26 min. The fluctuations in PP were less regular than and did not temporally correlate with the fluctuations in plasma levels of insulin, glucagon, or glucose (usual periods 8-12 min). 2) In human subjects the concentration but not the periodicity of PP was related to obesity. 3) Comparisons of simultaneously determined levels of PP in portal and central venous plasma of monkeys suggested that PP may be extracted to varying degrees by the liver, even under basal well-controlled conditions, and that neither the size of the PP portal-central gradient nor the period and amplitude of fluctuations was associated with PP concentration. We conclude that plasma PP levels fluctuate with such a large amplitude that these fluctuations must be considered in the interpretation of experimental results based on limited numbers of samples.
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PMID:Fluctuations in basal plasma levels of pancreatic polypeptide in monkeys and humans. 389 May 64

It is demonstrated that pre-obese Zucker rats, studied before weaning (17 days of age), at a time when they were indistinguishable from lean controls, do hypersecrete insulin in response to glucose or arginine administration when compared to their lean littermates in spite of normal basal insulin levels. When arginine is used as the stimulus, it is shown that pre-obese pups hypersecrete glucagon as well as insulin, the net result of insulin and glucagon oversecretion being probably the observed normoglycemia of these animals. Furthermore, these early substrate-induced increases in pancreatic hormonal secretion could be reduced toward normal values by acute pre-treatment of the pre-obese rats with the cholinergic inhibitor, atropine. It is suggested the parasympathetic nervous system plays a role in genetically obese fa/fa rats in bringing about an early increased substrate-induced insulin release, a defect which could be one of the causes involved in the development of their obesity syndrome. In adult animals, the involvement of the parasympathetic nervous system in insulin oversecretion is less clear probably due to the presence of an increased B cell mass. However, using three different experimental approaches, it could be seen that an increased vagal tone acting at the B cells in obese animals participate to their insulin hypersecretion.
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PMID:A role for the vagus nerve in the etiology and maintenance of the hyperinsulinemia of genetically obese fa/fa rats. 390 50

Twelve obese patients and 7 control subjects, age and sex matched, whose weights were greater than 200% of ideal weight and 100% of ideal body weight, respectively, underwent intravenous insulin and thyroid releasing hormone (TRH) tests. Serial prolactin growth hormone, insulin, blood sugar, cortisol, glucagon, thyrotropin stimulating hormone, thyroxine, and triiodothyronine were obtained by RIA. Obese patients showed no significant differences from controls in basal and nadir glucose, basal and peak glucagon, cortisol, and thyroid responses to both tests. Basal insulin levels were higher (36 +/- 9.4 vs 10 +/- 2.3 microU/ml, P less than 0.05) and peak growth hormone responses after insulin were lower in the obese group (6.1 +/- 1.1 vs 12.7 +/- 3.7 ng/ml, P less than 0.05) than in controls. Whereas all control subjects had prolactin responses to both tests, five of 12 obese patients had no responses to insulin. Obese patients had lower prolactin responses at 30 minutes after insulin (5.4 +/- 0.7 vs 12.9 +/- 3.7 ng/ml, P less than 0.05) and lower prolactin responses at 60 minutes after TRH (9.9 +/- 1.7 vs 20.4 +/- 5.9 ng/ml, P less than 0.05). Maximum prolactin responses after TRH were lower in obese patients (9.9 +/- 2.0 vs 28.8 +/- 10.9 ng/ml, P less than 0.05). Maximum prolactin responses after insulin were lower in obese patients (6.2 +/- 4.1 vs 28.9 +/- 18.3 ng/ml). Thus prolactin secretion in childhood obesity is decreased after both stimuli, but more so after IV insulin that TRH, and suggests that, as in adult hypothalamic obesity, neuroendocrine regulation of prolactin release in obese children is impaired.
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PMID:Decreased prolactin secretion in childhood obesity. 391 66


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