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

To investigate the alterations in insulin secretion induced by aging, 2-month-old, 12-month-old, and 12-month old lean rats (submitted to a caloric restriction during the last month that causes a weight loss of approximately 20%) were studied. As expected, glucose intolerance and increased insulin response were observed during IV-GTT in 12-month-old rats. These effects were, however, reversed by weight loss. Insulin secretion was investigated in isolated islets both during static incubation and perifusion. In 12-month-old rats insulin secretion and 45Ca2+ efflux were lower only in the second phase of the hormonal secretion, suggesting an involvement of voltage-sensitive calcium channels in these phenomena. Considering that in vivo and in vitro alterations were reversed after weight loss, it is possible to conclude that obesity is probably a major cause of impaired insulin secretion in 12-month-old albino rats. Since 14C-glucose metabolism was not changed in islets from aged rats, the effect of obesity on insulin secretion is not due to altered glucose metabolism in pancreatic B-cells.
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PMID:Obesity is the major cause of alterations in insulin secretion and calcium fluxes by isolated islets from aged rats. 132 24

A high plasma insulin concentration in the presence of a normal or high plasma glucose level appears to be a common feature of glucose intolerance, obesity, and hypertension. Hyperinsulinemia has been recognized as a major risk factor for the development of coronary artery disease independent of blood pressure and plasma lipid levels. All these conditions are frequently associated, particularly in aging, a state itself characterized by hyperinsulinemia. This common association has prompted the hypothesis that hyperinsulinemia may be a causative factor rather than the consequence of obesity, diabetes, hypertension, and hyperlipidemia. If that is the case, defining the nature and mechanisms of hyperinsulinemia becomes of primary interest. Insulin resistance is also a striking feature of all of the above mentioned pathologic states. In the presence of a preserved B-cell function, hyperinsulinemia can represent the mechanism designed to overcome the defect in the biological action of the hormone. For instance, there is a clear-cut age-related decline in the body's sensitivity to insulin. In order to compensate for this defect in insulin-mediated glucose metabolism, the B-cell must increase its secretion. On the other hand, a certain degree of insulin resistance can be induced both in animals and man by prolonged euglycemic hyperinsulinemia. Little is known regarding possible primary defects of the B-cell leading to uncontrolled oversecretion of insulin and subsequent insulin resistance. The primary defect, more probably, resides in an alteration of one or more of the steps whereby insulin exerts it own action. In favor of this hypothesis are the observations that insulin resistance segregates in familial clusters and that the first defect found in normoglycemic relatives of insulin-resistant diabetic patients is a reduced transformation of glucose into glycogen. Whatever is the primary defect, it is likely that a correction of insulin resistance might reduce the circulating levels of plasma insulin, possibly playing a beneficial effect on glucose tolerance, body weight, blood pressure and plasma lipid concentration.
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PMID:[Hyperinsulinism. Causes and mechanisms]. 133 21

Both haemodynamic and metabolic variables have been shown to be related to the fibre composition and capillary density of skeletal muscle in man. In the present study, the change of several metabolic variables during beta-blockade was investigated and related to muscle fibre composition and capillary density in 28 men with essential hypertension. They had been given atenolol (50 mg/day) or metoprolol (200 mg/day) or propranolol (160 mg/day) for 4-12 months. Serum triglycerides increased during treatment and individual changes were significantly inversely correlated with capillary density. Insulin concentrations in the fasting state and at the end of an i.v. glucose tolerance test were significantly higher during beta-blockade, and individual changes were inversely correlated with capillary density. Furthermore, body weight increased and heart rate decreased, changes that were also correlated with capillary density. It is concluded that many of the previously but poorly understood large interindividual differences in response to beta-blocker treatment may be explained by the degree of development of the capillary net in muscle tissue. Obesity, physical training as well as genetic factors are known determinants of capillary density.
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PMID:The metabolic and circulatory response to beta-blockade in hypertensive men is correlated to muscle capillary density. 136 76

Obese individuals are hyperinsulinemic and insulin resistant. Because amylin is cosecreted with insulin and may contribute to the insulin resistance of obesity, this study tested the hypothesis that insulin and amylin genes are coordinately regulated by obesity and carbohydrate feeding. Insulin and amylin gene expression were measured during the suckling/weaning transition in lean (Fa/Fa) and obese (fa/fa) Zucker rats, a period associated with marked changes in tissue insulin sensitivity. There was a decline in insulin mRNA (-90 +/- 15%, P less than 0.01) and amylin mRNA (-72 +/- 21%, P less than 0.01) content in pancreases of lean rats maintained on a high-fat diet from days 15 to 30, probably reflecting the relative increase in exocrine/endocrine development during this neonatal period and the effects of fat feeding. Weaning on high-carbohydrate versus high-fat diets resulted in enhanced expression of both insulin (P less than 0.05) and amylin (P less than 0.05) mRNAs. In contrast to the decline in pancreatic insulin and amylin mRNA content observed in lean rats, there was an increase in insulin mRNA (421.3 +/- 57.5%, P less than 0.05) and no change in amylin mRNA in obese rats maintained on a high-fat diet from days 15 to 30. There was no enhancement of insulin or amylin gene expression in obese rats with high carbohydrate relative to high-fat feeding, perhaps reflecting maximum rates of transcription in these obese insulin-resistant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Developmental regulation of amylin and insulin-gene expression in lean (Fa/Fa) and obese (fa/fa) Zucker rats. 137 76

Insulin is the principal regulator of hepatic insulin-like growth factor binding protein-1 (IGFBP-1) production, mediating the rapid decrease in plasma IGFBP-1 in response to nutritional intake. In this study, we defined IGFBP-1 regulation by insulin in upper and lower body obesity, conditions associated with insulin resistance and chronic hyperinsulinemia. Overnight postabsorptive IGFBP-1 levels in obese and nonobese women showed an inverse, nonlinear relationship with plasma insulin concentrations. Maximum suppression of IGFBP-1 was seen at 70-90 pmol/L plasma insulin. Both groups of obese women had mean fasting plasma insulin concentrations above this threshold level and, consequently, markedly suppressed IGFBP-1 levels. To assess the dynamics of insulin regulated IGFBP-1, 10 obese and 8 nonobese women were studied during sequential saline infusion (0-90 min), hyperinsulinemia (insulin infusion; 90-210 min) and hypoinsulinemia (somatostatin + GH infusion; 210-330 min). Insulin infusion rapidly decreased plasma IGFBP-1 levels in nonobese subjects (60% decrease in 2 h), but had little or no further suppressive effect in obese subjects. Complete insulin withdrawal resulted in a significant rise in plasma IGFBP-1 concentrations in all subjects, but the response was blunted in obese compared to nonobese groups. In contrast to plasma IGFBP-1, IGF-I concentrations did not vary during hyper- and hypoinsulinemic infusion periods and were not significantly different between groups. Basal GH levels were significantly higher in nonobese when compared to obese women, but did not change with infusions. In conclusion, low IGFBP-1 levels in obesity are related to elevated insulin levels which are, in turn, related to body fat distribution and insulin resistance. The chronically depressed levels of IGFBP-1 may promote IGF bioactivity as well as its feedback regulation of GH secretion, thus contributing to the metabolic and mitogenic consequences of obesity. In addition, our findings imply that hepatic insulin sensitivity in terms of IGFBP-1 production is preserved despite peripheral insulin resistance in obesity.
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PMID:Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. 137

The entry of glucose into muscle cells is achieved primarily via a carrier-mediated system consisting of protein transport molecules. GLUT-1 transporter isoform is normally found in the sarcolemmal (SL) membrane and is thought to be involved in glucose transport under basal conditions. With insulin stimulation, glucose transport is accelerated by translocating GLUT-4 transporters from an intracellular pool out to the T-tubule and SL membranes. Activation of transporters to increase the turnover number may also be involved, but the evidence is far from conclusive. When insulin binds to its receptor, it autophosphorylates tyrosine and serine residues on the beta-subunit of the receptor. The tyrosine residues are thought to activate tyrosine kinases, which in turn phosphorylate/activate as yet unknown second messengers. Insulin receptor antibodies, however, have been reported to increase glucose transport without increasing kinase activity. Insulin resistance in skeletal muscle is a major characteristic of obesity and diabetes mellitus, especially NIDDM. A decrease in the number of insulin receptors and the ability of insulin to activate receptor tyrosine kinase has been documented in muscle from NIDDM patients. Most studies report no change in the intracellular pool of GLUT-4 transporters available for translocation to the SL. Both the quality and quantity of food consumed can regulate insulin sensitivity. A high-fat, refined sugar diet, similar to the typical U.S. diet, causes insulin resistance when compared with a low-fat, complex-carbohydrate diet. On the other hand, exercise increases insulin sensitivity. After an acute bout of exercise, glucose transport in muscle increases to the same level as with maximum insulin stimulation. Although the number of GLUT-4 transporters in the sarcolemma increases with exercise, neither insulin or its receptor is involved. After an initial acute phase, which may involve calcium as the activator, a secondary phase of increased insulin sensitivity can last for up to a day after exercise. The mechanism responsible for the increased insulin sensitivity with exercise is unknown. Regular exercise training also increases insulin sensitivity, which can be documented several days after the final bout of exercise, and again the mechanism is unknown. An increase in the muscle content of GLUT-4 transporters with training has recently been reported. Even though significant progress has been made in the past few years in understanding glucose transport in skeletal muscle, the mechanisms involved in regulating transport are far from being understood.
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PMID:Regulation of glucose transport in skeletal muscle. 142 62

Serum C-peptide immunoreactivity (CPR)/immunoreactive insulin (IRI) molar ratio was determined in 136 subjects without renal, hepatic and thyroid disorders, at fasting, and during the initial period of 75 g-oral glucose tolerance test. The subjects were divided into 4 groups based on their body weight and age; Group A, young (< 55 years) and normal body weight (body mass index [BMI, kg/m2] < or = 25) subjects; Group B, young and overweight (BMI > 25) subjects; Group C, aged (> or = 55 years) and normal body weight (BMI < or = 25) subjects; Group D, aged and overweight subjects. Fasting CPR/IRI ratio and absolute CPR level negatively correlated in Groups B and D but not in A and C. After oral glucose load with elevation of insulin, CPR/IRI ratio invariably declined in all groups and significant negative correlation between CPR/IRI and CPR was found in Groups A, B and D but not in C. Slope of the regression lines obtained for correlation between CPR/IRI ratio and CPR were significantly steeper at fasting compared to the post-stimulation phase. CPR/IRI ratio is affected by hyperinsulinemia and oral glucose load but not by obesity alone. Assuming that CPR/IRI ratio reflects hepatic extraction of insulin, the insulin clearance at fasting is progressively reduced with increasing insulin secretion in overweight subjects: failure to detect such phenomenon in normal body weight subjects may be due to a narrower CPR range in this population. Insulin metabolism at fasting and during glucose stimulation is likely to be regulated by distinct factors.
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PMID:Differential effects of body weight, hyperinsulinemia and oral glucose load on serum C-peptide/insulin molar ratio. 142 14

The incidence of hypertension is increased in obesity, a state associated with an insulin resistance syndrome. By using an euglycemic clamp method, Ferrannini et al. demonstrated the existence of an insulin resistance state in patients with essential hypertension. However, the body mass index of the subjects studied appeared to be slightly excessive. This abnormality has not been observed in patients with secondary hypertension. Insulin resistance is probably localized to peripheral tissues such as muscles and may be associated with other cellular abnormalities. Can insulin resistance, characterized by a raised circulating insulin concentration in the presence of normal blood glucose, be responsible for certain "modifications" associated with essential hypertension? Insulin induces sodium retention and increases the aldosterone-secreting effect of angiotensin II. These effects are likely to promote a rise in blood pressure and an increase in the sensitivity of vessels to endogenous substances. Moreover, insulin is a known growth factor and is involved in lipoprotein metabolism. If insulin resistance plays an important role in the maintenance of complications of essential hypertension, it is important that the treatments used tend to correct this anomaly. Thiazide diuretics and beta-blockers aggravate insulin resistance while angiotensin converting-enzyme inhibitors correct this condition.
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PMID:[Arterial hypertension, hyperinsulinism and insulin resistance]. 143

The effect of varying degrees of hyperglycaemia on insulin secretion was studied in newly diagnosed non-insulin dependent diabetic patients, stratified according to the fasting plasma glucose values. Of the 116 patients studied, 62 were non-obese and 54 obese. Insulin response patterns during 2h oral glucose tolerance test were analysed in comparison with the values in weight matched control subjects and also with respect to the degree of hyperglycaemia. The effect of hyperglycaemia on beta cell secretion differed in obese and non-obese patients. In the non-obese, fasting insulin levels were within normal range even in those with severe hyperglycaemia while the corresponding values in response to glucose stimulation showed a decreasing pattern. In obese patients, even fasting immunoreactive insulin (IRI) value was decreased and with increasing hyperglycaemia the reduction in IRI response to glucose stimulation was of greater magnitude compared to non-obese patients. Thus the modulating effect of obesity on insulin secretion appears to disappear with development of hyperglycaemia. The insulinogenic index was low in all the diabetic patients.
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PMID:Insulin responses to varying hyperglycaemia in newly diagnosed non-insulin dependent diabetic patients. 145 31

Hypertensive obese subjects run an increased cardiovascular risk. Their predominantly abdominal obesity is often associated with hypertriglyceridaemia and insulin-resistant diabetes, and their cardiovascular status is characterized by cardiac hyperdynamics and hypervolaemia responsible for left ventricular hypertrophy and dilatation. Insulin resistance and subsequent hyperinsulinaemia are thought to explain the obesity-hypertension association, the cardiovascular effects observed and the metabolic and cardiovascular complications which might result from this situation. Successful control of both arterial pressure and overweight should contribute to regression of the left ventricular hypertrophy. Simultaneous treatment of abnormalities in carbohydrate and lipid metabolism is also necessary to prevent cardiovascular complications.
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PMID:[Cardiovascular consequences of obesity associated with arterial hypertension]. 146 76


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