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

An account is given of the present conception of asymptomatic (chemical) diabetes in the pediatric age group, which also has been named MODY (maturity-onset type of diabetes of young people). Long-term studies show that about 10% will eventually decompensate to overt diabetes. In contrast to classical juvenile-onset type of diabetes the inheritance of MODY seems to be autosomal dominant in many cases. Some authors have suggested that insulin resistance exists in non-obese patients with asymptomatic diabetes, but this view is not supported by observations of the author. Obese patients should reduce their body fat, but other therapeutic approaches are difficult to evaluate because of the normal fluctuation of the disease. There is no general agreement in the literature concerning the value of insulin treatment. The author supports the view that insulin treatment should be started in the late stages of chemical diabetes just before symptomatic disease emerges. In the long run this approach may ameliorate the condition due to the preservation of some beta-cell function for long periods. An unsettled question is whether early insulin treatment in asymptomatic diabetes will delay diabetic vascular complications.
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PMID:Asymptomatic diabetes in childhood and adolescence. A review. 35 15

It has been considered that hyperinsulinemia is one of the important factors in the development of obesity. With the purpose of investigating the mechanisms of hyperinsulinemia in obese rats induced by hypothalamic lesions (HTL), the time-caused changes in body weight, blood glucose and plasma immunoreactive insulin (IRI) levels in addition to histological changes in the pancreatic islet were studied. The following results were obtained. 1. The development of obesity, a rise of plasma IRI level and an enlargement of pancreatic islets were found in HTL rats. The enlargement of pancreatic islets was directly proportional to body weight, index of obesity and plasma IRI level. 2. The B cells of the pancreatic islets of HTL rats revealed well-developed Golgi apparatus and rough endoplasmic reticulum, and numerous degranulated and pale secretory granules. 3. A number of mixed cells were shown in the periphery of the pancreatic islets of HTL rats. 4. Emiocytotic phenomena of the granular discharge were encountered frequently in the B cells of the pancreatic islets of HTL rats. These histological findings of the B cells in HTL rats well reflected hypersecretion of insulin in this type of obesity.
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PMID:[Histological study of pancreatic islets in hypothalamic obese rats (author's transl)]. 36 46

The authors examined 48 patients with different endocrine pathology (relatives of patients with diabetes mellitus with a normal glucose tolerance test, patients with diabetes mellitus, obesity, thyrotoxicosis, and hypothyroidism) and a group of healthy persons. Blood glucagon concentration was determined radioimmunologically on fasting stomach and against the background of insulin hypoglycemia. A marked reduction of glucagon on fasting stomach was noted in patients with diabetes mellitus, and a reduction of the hormone concentration 30 and 60 min after the insulin injection. In obese patients and relatives of diabetic patients the initial blood glucagon level was not different from that in healthy persons. At the same time there was a significant reduction, and in relatives of diabetes patients also a retardation of glucagon secretion against the background of insulin hypoglycemia. The pattern of glucagon secretion in thyrotoxicosis and hypothyroidism proved to be changed.
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PMID:[Glucagon secretion in several endocrine diseases]. 36 65

A longitudinal in vivo and in vitro analysis of the genesis of insulin resistance has been carried out in mice made obese by chemical made obese by chemical lesion (goldthioglucose, GTG) of the hypothalamus. Six weeks after GTG administration, glycemia and glucose disposal were normal but associated with increased insulin concentration, suggesting incipient insulin resistance. The in vitro counterpart of the latter in obese mice was observed in soleus muscle that was somewhat less responsive to insulin than controls, in liver that had increased basal lipogenesis but was uninfluenced by insulin, and in hepatic plasma membranes in which a slight decrease of insulin binding was measured. At this stage of obesity, basal adipose tissue lipogenesis was increased but the tissue responded in a normal fashion to insulin. These relatively discrete early metabolic changes were corroborated in vivo by a normal hypoglycemic effect of exogenous insulin. Sixteen weeks after GTG administration, hyperglycemia and gross hyperinsulinemia were recorded. This insulin resistance was evidenced in vivo by the lack of hypoglycemic effect of exogenous insulin unless considerable amounts of the hormone were administered. It coincided in vitro with a poor response of soleus muscle to insulin, an absence of a stimulatory effect of the hormone upon both adipose tissue and liver tissue, and a marked decrease in insulin binding to liver plasma membranes. It appears that insulin resistance is a multifactorial and progressive abnormality that might involve both insulin receptor and intracellular metabolic alterations.
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PMID:Longitudinal study on the establishment of insulin resistance in hypothalamic obese mice. 36 21

The kinetics of unlabeled porcine insulin were studied in 69 nondiabetic male subjects aged 18-83 yr with obesity indexes of 0.93 - 1.51 and in 12 maturity-onset diabetics age 46-78 yr with obesity indexes of 0.95-1.56 by using the euglycemic clamp technique. Analysis of the insulin kinetic data by using a mathematical model permitted the determination, for each individual, of steady state distribution masses and degradation rate constants. The individuals were grouped to allow comparison of the results on the basis of age, obesity index, or diabetes. The responses over a period of 120 min to an infusion and wash out of insulin show some transient as well as steady state differences with age, obesity, or diabetes. Analysis of these data by use of compartmental models leads to the conclusion that in the steady state the ratio of insulin in extravascular spaces to that in plasma (T/P) is decreased in the moderately obese group (26%) and in the diabetic group (17%) but increased in the older group (13%) when each is compared with the appropriate control. Since extravascular insulin includes both insulin bound to receptors and insulin in the interstitial fluid, the observed changes in the extravascular to plasma mass ratio most likely reflect changes in in vivo binding to receptors, although the magnitude of the change would be modified somewhat by changes in the size of the interstitial spaces relative to plasma. In addition, the rate of entry of new insulin into plasma (BSDR) was increased in the diabetic population (45%; P less than 0.02) as well as in the moderately obese group (27%) but was decreased somewhat in the older group (11%). The following general conclusions can be drawn from the results: The pattern of parameter changes seen with obesity is similar to that seen with maturity-onset diabetes. The decrease in T/P seen with obesity and with maturity-onset diabetes cannot be accounted for solely by changes in fasting plasma insulin levels in these populations. The pattern of changes seen in the older subjects is opposite that seen in the maturity-onset diabetics, which suggests that diabetes is a perturbation distinct from the normal aging process. Finally, the changes in the metabolism of insulin are not large, making it unlikely that they are the sole cause of the major alterations in glucose tolerance seen with aging, obesity, or diabetes.
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PMID:Kinetics of native insulin in diabetic, obese, and aged men. 36 27

Obesity in the Zucker rat is accompanied by hyperlipemia, hyperinsulinism, insulin resistance, pancreatic hyperplasia, and islet hypertrophy. This study correlates the morphologic heterogeneity of isolated pancreatic islets with secretion of insulin and glucagon in the perifusion system. Islet size was arbitrarily defined as large (greater than 0.45 mm) or small (smaller than 0.12 mm). Protein content and volume (V = 4/3pir3) were calculated for groups and individual islets, respectively. Islets from obese rats secreted more insulin in response to glucose and aminophylline than islets from lean rats (peak 7.8 +/- 2.4 vs. 1.5 +/- 0.37 microU/islet/min, P less than 0.005). Insulin release was related directly to islet size and protein content. Small islets from lean and obese animals produced less insulin per islet than large islets (P less than 0.005). In terms of islet volume, however, large islets were inefficient insulin releasers as compared to small islets (P less than 0.005). Stimulation with Br-cAMP released glucagon from islets of lean but not from large islets of obese animals (peak 11 +/- 3.3 vs. 4.1 +/- 0.3 pg/microgram protein per minute, P less than 0.05). Arginine produced the same effect on glucagon release (P less than 0.05) as stimulation with Br-cAMP. The observed increased insulin release rates and the blunted glucagon response are related to islet size in the pancreas of the Zucker rat.
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PMID:Correlation between morphology and function in isolated islets of the Zucker rat. 37 79

The pituitary glands from mice rendered obese by gold thioglucose treatment and by dietary manipulation, and pituitary glands from lean mice after a high food intake or a glucose load, were shown to stimulate insulin secretion from isolated pancreatic islets. The insulin releasing activity of pituitary glands from obese (ob/ob) mice was reduced by fasting for 24 and 48 h. Results obtained with pituitary glands from ob/ob and from lean ob/+ and +/+ mice suggest that the insulin releasing property manifests a gene dosage effect. Pituitary glands from 3-week-old (young) ob/ob mice stimulated insulin secretion to the same extent as pituitary glands from 3-month-old (adult) ob/ob mice. The pancreatic islets of young ob/ob mice were shown to be somewhat more responsive to stimulation by the pituitary factor than were lean ob/+ or +/+ islets from this age group. The concept that high insulin level, partly under pituitary control, and high caloric intake may be interlinked and may, in combination, be a major factor in producing obesity is discussed. Furthermore, it is suggested that the pituitary insulin releasing factor may play a role in the early development of obesity in the animal models studied.
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PMID:Acute regulation of insulin release by the pituitary gland in relation to hyperinsulinaemia and obesity. 38 64

Genetically or experimentally-produced (e.g. via lesions of the hypothalamus) obese animals have several common features such as increased hepatic lipogenesis (resulting in fat infiltration) and increased hepatic lipoprotein secretion, together, with increased adipose tissue lipogenesis. These abnormalities appear to be related primarily to hyperinsulinemia as they are reversed to or toward normal when hyperinsulinemia is corrected or, conversely, as they develop concomitantly with hyperinsulinemia. In the liver (ob/ob mice), another defect can be demonstrated, i.e. a decreased hepatic insulin clearance. This defect is also related to hyperinsulinemia and is markedly reduced upon normalizing hyperinsulinemia of obese mice. Hyperinsulinemia may thus be a key feature of the obesity syndromes, and bring about most of the abnormalities noted, including the subsequent state of insulin resistance known to exist in obese animals. The etiology of hyperinsulinemia of genetically obese animals is still unknown. Among the possible mechanisms one should cite possible primary dysfunction of the pancreas, possible primary dysregulation, by the hypothalamus, of overall endocrine pancreas activity.
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PMID:Animal obesities. 38 57

This review begins with James Olds' discovery that self-stimulation at various brain sites can be influenced by food intake or androgen treatment. It then describes our research designed to reveal the functional significance of self-stimulation. The evidence suggests that lateral hypothalamic self-stimulation is controlled by many of the same factors that control feeding. We believe this control is exerted by at least two neural mechanisms. One is the classical, medial hypothalamic satiety system. Another is an adrenergic system ascending from the midbrain to the lateral hypothalamus. Damage to either one can disinhibit self-stimulation and feeding, thus contributing to obesity. Some of our studies use rats with two electrodes, one that induces feeding and one that induces mating. There are two response levers in the test cage, one for self-stimulation and one for escape from automatic stimulation. With the feeding electrode, rats self-stimulated less and escaped more after a meal than before. The same shift occurred after an anorectic dose of insulin or the commercial appetite suppressant phenylpropanolamine. With the sex electrode the shift from reward to aversion occurred after ejaculation. The review ends with credit to James Olds for pioneering this line of research into the neuropsychology of reinforcement.
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PMID:Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating. 38 51

Based on the consideration that insulin does not act directly on metabolic processes but affects membrane carriers and key-enzymes that regulate metabolic pathways, determination of insulin responsiveness of the various key-enzymes is suggested as a very appropriate method for studying insulin resistance. Insulin resistance, as it occurs in obese or obese-diabetic humans and animals, is most often associated with hyperinsulinemia, and is characterized not only by increased activity of key-enzymes of pathways known to be stimulated by insulin (glycolysis, lipogenesis), with the possible exception of glycogen synthesis, but also by a trend towards increased activity of key-enzymes of 'catabolic pathways', normally depressed by insulin. In the adipose tissue there is a normal-to-enhanced basal lipolysis, which in man would result from the prevalence of the active over the inactive form of triacylglycerol lipase. In muscle, the increased amino-acid release that can be inferred from the elevated blood level of both alanine and branched-chain amino acids suggests an enhanced proteolysis. In liver, there is an elevation in the activity of the key gluconeogenic enzymes, which forms the basis of the augmented gluconeogenesis. In both muscle and liver, phosphorylase is also elevated with no change in glycogen synthase. Therefore, insulin resistance seems to consist of the failure of insulin to depress the key-enzymes of catabolic pathways. Possible resistance of glycogen synthetase, which might account for decreased glucose utilization in muscle, may be due to the opposing effects of the phosphorylation process on glycogen synthetase and phosphorylase, implying that activation of phosphorylase (which occurs in obesity) entails inhibition of the synthetase. The fact that insulin insensitivity concerns only the 'catabolic' but not most 'anabolic' pathways makes it unlikely that the unresponsiveness is due to a reduction in insulin receptors or increase in insulin degradation. Since resistance to insulin is shown by enzymes regulated by such different mechanisms as induction-repression (gluconeogenic enzymes), covalent modifications (lipase, phosphorylase), and changes in lysosome stability (lysosomal proteases responsible for proteolysis, a single basic mechanism for explaining insulin insensitivity cannot be envisaged at present.
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PMID:Insulin resistance in obesity: a critical analysis at enzyme level. A review. 39 47


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