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

The hormone-substrate milieu has been investigated in male fasted lean (C57BL/6-+/+) mice and mutant obese mice of the same strain (C57BL/6-obob). The lean mouse, in winter, mobilized insufficient fat (due to inadequate stores) to permit survival beyong 3 days and was unable to achieve any degree of conservation of vital protein stores. By contrast, in summer, the same animals survived 7 days and showed evidence of greater and more sustained fat mobilization and ketosis and the ability to conserve protein. The insulin, glucagon, and insulin/glucagon molar ratios changed in both groups in a direction consistent with conversion to a catabolic state, and hence were probably largely responsible for the mobilization of substrates and stimulation of gluconeogenesis and ketogenesis. The seasonal difference in response is unexplained. The obob mice, generally employed as a model for obesity, hyperglycemia, and hyperinsulinemia showed these features but also adapted to fasting in a fashion permitting prolonged survival during this state. In a fashion analogous to that known to occur in man, these animals developed fall in glycemia, rise in circulating fat-derived substrates, and marked protein conservation. Profound fall in insulinemia was associated with a fall in glucagonemia, the latter from normal levels. Thus the initial markedly "anabolic" insulin/glucagon molar ratio diminished, but nevertheless remained higher than at any time in the lean mice. Pancreatic contents of insulin showed markedly different changes with fasting in obob compared with lean mice. The ability of the obese mouse to adapt to prolonged fasting in a fashion largely analogous to that of man renders it a useful model for the study of metabolism in this state, with the potential of applicability of findings to man.
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PMID:Hormone-substrate responses to total fasting in lean and obese mice. 109 42

By mating mice heterozygous for the recessive gene, obese (ob/+) (+/+), with mice homozygous for the recessive gene, dwarf (+/+)(dw/dw), and subsequent mating of the offspring, mice homozygous for both the obese and dwarf gene were obtained. It was established that the genes for obese and dwarf mice belong to different linkage groups. The homozygous obese dwarf mice develop obesity and hyperinsulinemia. The degree of hyperglycemia developed by these homozygotes is not significantly different from that of nonobese dwarf mice. Because homozygous dwarf mice are deficient in growth hormone production, it was concluded that obesity and hyperinsulinemia can develop under conditions of extreme growth hormone deficiency.
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PMID:Development of the obese-hyperglycemic syndrome in mice with a growth hormone deficiency. 112 28

The prevalence of coronary risk factors was assessed in 1,817 asymptomatic adults in Long Beach, California, at the beginning and end of a 10-11 month interval. The risk factors evaluated were hypercholesterolemia, hypertriglyceridemia, hypertension, smoking, hyperglycemia, and marked obesity. The results of the tests were sent to the participants and to their physicians. An educational program aimed at reducing coronary risk factors was offered to the first 1,250 persons screened. Eight hundred and seventy-two of those 1,250 allocated to the education group returned for a second screening. The prevalence of 0, 1, 2, 3, 4, 5, or 6 coronary risk factors did not change significantly between the two screens in either the total group of 1,817 adults or in the 872 adults in the educational program. The Long Beach Heart Association mass screening program for coronary risk factors was ineffective in reducing the number of coronary risk factors.
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PMID:Follow-up of mass screening for coronary risk factors in 1817 adults. 113 94

Insulin-carbohydrate relationships were investigated in four groups of young rats fed low protein diets differing in carbohydrate and fat contents: (1) a diet in which the nonprotein energy was provided by fatty acids (FA); (2) a similar diet in which the fatty acids were substituted by neutral fat (NF); (3) FA diet supplemented with glycerol (FA-Glyc); and (4) a carbohydrate-rich diet (HC). Control rats were fed a stock diet. Rats fed the FA diet lost weight, were hypoglycemic and hypoinsulinemic in the fed state and normoglycemic and normoinsulinemic in the fasted state, and had an impaired glucose tolerance and hyperinsulinemia after a glucose load. Liver and muscle glycogen were low in fed rats. Fasting increased glycogen in liver and decreased glycogen in muscle. NF animals gained weight, were hypoglycemic in both fed and fasted states, and their plasma glucose level after an oral glucose load was almost normal. Plasma insulin/glucose ratio, both in fed and fasted states and after a glucose load indicated hyperinsulinism, which was accompanied by obesity. Muscle and liver glycogen were low in fed animals and did not change after a fast. Supplementation of the FA diet with glycerol (FA-Glyc) abolished weight loss and fasting hyperglycemia and normalized plasma glucose and insulin response to a glucose load. Rats fed the HC diet had an improved glucose tolerance and an increased sensitivity to insulin. Liver glycogen was high in the fed state and normal in the fasted state, whereas muscle glycogen was normal in both nutritional states.
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PMID:Effects of carbohydrate-free diets on the insulin-carbohydrate relationships in rats. 115 29

The role of insulin in the regulation of human adipose tissue lipoprotein lipase was evaluated. Adipose tissue heparin-releasable lipoprotein lipase (thought to be related to peripheral clearance of plasma triglycerides) was low in insulin-deficient, untreated hyperglycemic diabetic subjects (P less than 0.001) and treatment of hyperglycemia returned the activity to normal. In chronic hyperinsulinism, represented by obesity, heparin-releasable activity among control subjects was correlated to percent of ideal body weight (r=0.53, P less than 0.05) and to fat cell size (r=0.61, P less than 0.02). Acetone-ether powder lipoprotein lipase activity (presumed to reflect total tissue enzyme) was also related to percent of ideal body weight (r=0.76, P less than 0.001 for controls; r=0.67, P less than 0.05 for diabetics) and to fat cell size (r=0.71, P less than 0.01 for controls; r=0.85, P less than 0.01 for diabetics. Postprandial-stimulated insulin secretion was related to diet-induced changes in lipoprotein lipase in control subjects; both were dependent upon the amount of dietary carbohydrate. In contrast, the diabetic patients with low insulin responses, failed to increase lipoprotein lipase activity with feeding. The changes in heparin-releasable (r=0.66, P less than 0.01) and acetone-ether powder (r=0.69, P less than 0.01) activity during feeding were related to the percent increase in plasma insulin. Thus, insulin appears to be important in the regulation of human adipose tissue lipoprotein lipase activity. Elevated insulin levels in obesity and increased insulin secretion after eating were associated with increased lipoprotein lipase activity. Defects in insulin secretion, both in postabsorptive and postprandial states, are associated with low adipose tissue lipoprotein lipase and may lead to hypertriglyceridemia in diabetic man.
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PMID:Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity. 118 38

The insulin response to an oral glucose load (100 gm.) in 127 patients with a previous myocardial infarction (MI) (six months to one year) and in 65 patients with surgically treated or arteriographically identified peripheral vascular disease (PVD) was compared with that of 89 controls after matching the three collectives for age, glucose tolerance, and per cent ideal body weight (% IBW). The insulin response was of greater magnitude in MI and PVD groups than in respective control groups also in the absence of hyperglycemia, hypertriglyceridemia, and obesity. This finding suggests that hyperinsulinism may represent an early metabolic alteration associated with the development of MI and PVD. The insulin secretion pattern was prevalently of the delayed type in association with impaired glucose tolerance and with hypertriglyceridemia but not with overweight. Correlations between serum insulin, triglyceride (TG) levels, and % IBW were also investigated. We found a strong correlation (p less than 0.001) between stimulated insulin levels and % IBW in MI patients and none in PVD patients; conversely, the correlation between serum insulin and TG levels was very high (p less than 0.001) in PVD patients and only weak (p less than 0.05) in MI patients. No correlation was found between cholesterol (CH) levels and any of the other parameters studied. According to these results, it seems likely that hyperinsulinism plays a major role as a closely associated factor to obesity in those subjects who develop an MI, whereas in PVD patients the raised insulin levels may favor lipid accumulation in the arterial intima and accelerate the progress of atherosclerosis.
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PMID:Insulin response to oral glucose in patients with a previous myocardial infarction and in patients with peripheral vascular disease. Hyperinsulinism and its relationships to hypertriglyceridemia and overweight. 127 7

The adipocyte membrane G protein pattern, beta-adrenergic receptor activity, and adenylyl cyclase were determined in adipocyte membranes of the db/db mouse, a mutant that is a model of diabetes preceded by hyperinsulinemia, hyperglycemia, and extreme obesity. These studies were undertaken to determine whether the alterations already noted in the ob/ob mouse and those in the db/db mouse are similar and related to the hormonal defects, particularly the hyperinsulinemia and hyperglycemia prevalent in these animals (cf. Ref. 11). The ADP ribosylation data show that Gs alpha was more highly labeled in the tissues of the db/db mutant than in the homozygous control, but there was no significant difference in the amount of ADP-ribose incorporated in the Gi alpha-subunits. Quantification of the proteins by immunodetection revealed that the long (46-kDa) form of Gs alpha was significantly less abundant in the db mutant than in its control, whereas there was no difference in the short (42-kDa) form. Gi alpha-peptides corresponding to Gi alpha 2 and Gi alpha 1 were both less abundant in the db mutant than in the homozygous control. These data contrasted with those obtained for ob mutants and their lean homozygous controls reported previously (4) and confirmed here. It is concluded on the basis of these studies that factors other than the hormonal status are responsible for the G protein patterns in the ob and db mutants. Differences in G protein patterns noted in between the control groups (B/Ks or B/6 homozygotes) correlated strongly with the quantitative differences in adenylyl cyclase response in the two strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-subunits of Gs and Gi in adipocyte plasma membranes of genetically diabetic (db/db) mice. 132 37

The circadian rhythm of glycogen metabolism in liver and skeletal muscle was studied in lean and gold thioglucose (GTG) induced-obese mice. The active forms of glycogen synthase (GSI) and phosphorylase (GPa) and the total activity of these enzymes were measured every three hours over a 24 h period in mice fed ad libitum. Hepatic and muscle glycogen content displayed a marked diurnal rhythm that was similar in lean and obese mice. In skeletal muscle the glycogen content, GSI and GPa were not significantly different in lean and obese animals over the 24 h period. The activities of muscle GSI and GPa were constant in both groups despite the diurnal variation in the muscle glycogen content. The absence of an increase in the glycogen content of skeletal muscle despite the pronounced hyperinsulinemia and hyperglycemia in the obese mice, may indicate the degree of insulin resistance in this tissue or the maximal capacity of muscle tissue to store glycogen. In liver, glycogen concentration and total glycogen storage were higher in obese mice. Unlike muscle, both hepatic GSI and GPa underwent significant changes in activity over the 24 h period. Hepatic GSI was lower and GPa was higher in obese mice. The circadian rhythm in enzyme activities was independent of both blood glucose and insulin levels. The total glycogen storage and the activities of total phosphorylase and GPa were significantly increased in the liver from GTG obese mice over a 24 h period and could be implicated in the development of insulin resistance and glucose intolerance in this model of obesity.
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PMID:Diurnal rhythms of glycogen metabolism in the liver and skeletal muscle in gold thioglucose induced-obese mice with developing insulin resistance. 133 47

Fenfluramine improves glucose tolerance in obese subjects independently of its anorectic effect. Increased insulin action has been reported, but such an effect may be secondary to reduced hyperglycemia following augmented insulin secretion. For this reason, we investigated whether the dextro-enantiomer of fenfluramine (dexfenfluramine, dF) has a direct effect on insulin secretion using the glucose infusion test, a technique that can also be used to indirectly evaluate insulin action. Ten lean controls (BMI 21 +/- 0.4 kg/m2), 9 non-diabetic obese subjects (BMI 32.3 +/- 1.1) and 10 obese mild non-insulin dependent diabetics (BMI 36 +/- 2.6, fasting plasma glucose (FPG) 7.9 +/- 0.9 mmol/l) were studied with a random, double blind cross-over protocol. Each subject received 15 mg dF (or placebo) twice daily for 3 days prior to glucose infusion; 30 mg dF (or placebo) were given 90 min before the test. Obese control and diabetic subjects continued treatment with either dF or placebo for one month after which they were retested. There was no significant change in weight or fasting plasma glucose or insulin in any group. Biphasic insulin secretion was demonstrated in both non-diabetic groups, whereas a complete lack of first-phase and a delayed and reduced second phase insulin response was demonstrated in the diabetic subjects. There was no acute or chronic (obese subjects) effect of dF on insulin secretion in any group. In lean control subjects, plasma glucose curves during glucose infusion were unchanged by dF, whereas in non-diabetic obese subjects the glucose slope was improved after both acute and chronic dF, implying augmented glucose disposal. In diabetic patients, no significant acute or chronic effect of dF on glucose response was registered. When all obese subjects were re-grouped according to fasting plasma insulin levels (FPI) and not glucose tolerance, those with relative fasting hyperinsulinemia (> 100 pmol/l, mean +/- SE = 144 +/- 12 pmol/l) showed significant improvement of insulin action after dF, whereas those with low FPI (< 100 pmol/l, mean +/- SE = 65 +/- 7 pmol/l) did not. These findings, together with previously published results of improved insulin action in diabetics during hyperinsulinemic clamps, suggest that dF-mediated improvement in glucose clearance may require substantial plasma insulin concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute and chronic effects of dexfenfluramine on glucose and insulin response to intravenous glucose in diabetic and non-diabetic obese subjects. 134 13

Lipoprotein(a) [Lp(a)] has been added to the list of independent risk factors for cardiovascular disease (CVD), whose incidence is greater in obese subjects. There are few data available on the serum Lp(a) concentrations in obese individuals with or without insulin dependent diabetes mellitus (NIDDM). We selected 31 obese men with normal glucose tolerance (NGT) tests, 15 obese diabetic men, 14 non obese diabetic men and 17 healthy men as controls. We measured serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin and Lp(a). The mean Lp(a) levels in NGT obese men were 70.00 +/- 13.40 mg/l, which were similar to those found in normal controls (75.98 +/- 24.70 mg/l); significantly higher mean Lp(a) levels were found in obese diabetic men (168.84 +/- 56.43 mg/l) and in non obese diabetic men (240.85 +/- 63.35 mg/l). No significant correlation between Lp(a) levels and age, body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, insulin, was found; only a significant positive correlation between Lp(a) levels and glucose could be revealed (P < 0.05). Since higher levels of Lp(a) were found in NIDDM subjects with or without obesity, we conclude that hyperglycemia may influence the levels of serum Lp(a) facilitating its glycosylation in the liver with the consequence of a decline in its catabolic rate.
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PMID:Serum lipoprotein Lp(a) in obesity. 134 6


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