UMLS:C0028754 - FACTA Search

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

Recently, a missense mutation replacing tryptophan with arginine at codon 64 of the beta 3-adrenergic receptor gene was shown to be associated with insulin resistance in nondiabetic subjects and to an earlier onset of NIDDM in Pima Indians. We studied whether the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene in a cohort of young healthy Danes was associated with high birth weight, accelerated weight gain during childhood and adolescence, present obesity, or impaired insulin sensitivity. The protocol included 380 unrelated white subjects in whom insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test. A number of biochemical and anthropometric characteristics were determined for each subject. The subjects were genotyped for the codon 64 polymorphism by applying polymerase chain reaction restriction fragment-length polymorphism screening with the use of endonuclease BstN1. The allelic frequency of the mutated allele was 7% (95% CI: 5-10%), and it was similar in obese and nonobese subjects. The beta 3-adrenergic receptor gene variant was not related to birth weight or weight gain during childhood or adolescence. In its heterozygous form, the gene variant was not associated with an altered insulin sensitivity index (SI) or other features of the insulin resistance syndrome (BMI, blood pressure, fasting serum lipid levels, or fasting serum fibrinolytic variables). Three homozygous carriers of the polymorphism were identified, and each had a significantly higher BMI (27.4 +/- 1.3 vs. 23.5 +/- 3.7 kg/m2 [mean +/- SD]; P = 0.032), lower SI [4.9 +/- 2.9 vs. 15.4 +/- 9.0 10(-5) x (min x pmol/l)-1; P = 0.013], and higher fasting serum C-peptide (730 +/- 155 vs. 471 +/- 158 pmol/l; P = 0.016) than the wild-type carriers. The homozygous carriers also had significantly higher levels of fasting serum triglyceride (P = 0.042) and serum LDL cholesterol (P = 0.013). When adjustments were made for age, sex, BMI, and VO2max in a multiple regression analysis, a significantly negative association was found between homozygosity for the codon 64 variant and the SI (P = 0.009). We conclude that in young healthy Danes, the homozygous form but not the heterozygous form of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor may be associated with obesity and, independent of BMI, with a low SI. Since only three homozygous carriers were identified among 380 subjects, the results must be interpreted with caution, and studies of larger population samples are needed.
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PMID:Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene. 869 Jan 60

The reported prevalence of type 2 diabetes among the Kuwaiti population varied from one source to another. This study was undertaken to define the magnitude of the problem and to suggest plans for future diabetic care. All type 2 Kuwaiti diabetic subjects registered and continuing to attend regularly in two health areas Mubarak Health Area (MHA) and Farwania Health Area (FHA)] were selected for the study. There were 3222 in MHA and 5114 in FHA among the Kuwaiti population aged 20 years and above, accounting for a total crude prevalence of 7.6% in both health areas and for a prevalence rate of 5.6% in MHA and 10.0% in FHA. The age-specific prevalence of type 2 diabetes in both areas combined rose from 2.639 per 100 population in the age group 20-39 years to 15.350% and 26.252% in the age groups 40-59 and 60 and above, respectively. The female to male ratio was 1.7, 1.6, 1.1, respectively, in MHA and 1.7, 2.0, 0.9 in FHA for the age groups 20-39, 40-59, and 60 and above. This study shows that type 2 diabetes is a major public health problem in Kuwait, with a female preponderance. Obesity is a characteristic feature of the population studied, with a mean body mass index of 31.8 +/- 6.3 and 28.5 +/- 5.1 in women and men, respectively. A positive family history of diabetes mellitus was reported in 63% of the diabetic subjects. There is a need to standardize methods of reporting and to plan a national screening survey.
Acta Diabetol 1996 Jul
PMID:Known type 2 diabetes mellitus among the Kuwaiti population. A prevalence study. 887 Aug 17

Polymorphic variation of genes encoding the glucose transporters glycoproteins (GLUT) may contribute to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes. In this study we evaluated the allele and genotype frequencies of GLUT1 and GLUT4 restriction fragment length polymorphism (RFLP), revealed by digestion with XbaI for GLUT1 and KpnI for GLUT4, in Caucasian, Chinese, Japanese, Asian Indian and American black populations. No differences of the KpnI GLUT 4 RFLP were found between control and diabetic subjects in any ethnic group or when all data are combined. In contrast, positive results were found for the XbaI RFLP: (1) most ethnic groups showed an association of allele 1 with type 2 diabetes, and this association was maintained when all groups were analysed together; (2) after stratifying for sex and obesity, this association was significant only for overweight/obese women. This joint analysis suggests that GLUT1 polymorphism may contribute to susceptibility to type 2 diabetes in some populations, and especially in overweight/obese women.
Acta Diabetol 1996 Sep
PMID:Genetic contribution of polymorphism of the GLUT1 and GLUT4 genes to the susceptibility to type 2 (non-insulin-dependent) diabetes mellitus in different populations. 890 24

A sample taken from a population (Maltese) with a high incidence of the metabolic complications of central obesity was studied to determine: (1) whether the standard Schofield equations adequately predict the basal metabolic rate (BMR) in this population; (2) whether the Maltese have a greater tendency for central obesity compared with other populations; (3) whether the distribution of body fat influences energy expenditure and fuel selection. Healthy women responding to a public advertisement were sampled randomly from the Maltese population. Correlation analysis and analysis of variance were used to study relationships between BMR and body composition. Anthropometric parameters (including body fat distribution indices, bioimpedance) and BMR were measured after an overnight fast. Six percent of the respondent were excluded because of recent illness, instability of diet or of body weight. Fifty subjects attended a clinic at the Medical School. The distribution of excess fat between central and peripheral areas in the Maltese population was similar to that reported for the British population. The Waist-hip ratio (WHR) reflected neither basal heat production (BMR) nor the contribution of fat oxidation to BMR. The Schofield equations systematically underestimated BMR by 5.4% +/- 0.86% (P < 0.05). The study suggests a limitation in using the Schofield equations for predicting BMR in the female Maltese population studied. It also suggests that the fat distribution between central and peripheral areas in this population has no effect on BMR.
Acta Diabetol 1996 Sep
PMID:Relationship between anthropometric indices of body fat distribution and basal energy metabolism in healthy Maltese women. 890 25

In the genetic mutant mouse models ob/ob or db/db, leptin deficiency or resistance, respectively, results in severe obesity and the development of a syndrome resembling NIDDM. One of the earliest manifestations in these mutant mice is hyperinsulinemia, suggesting that leptin may normally directly suppress the secretion of insulin. Here, we show that pancreatic islets express a long (signal-transducing) form of leptin-receptor mRNA and that beta-cells bind a fluorescent derivative of leptin (Cy3-leptin). The expression of leptin receptors on insulin-secreting beta-cells was also visualized utilizing antisera generated against an extracellular epitope of the receptor. A functional role for the beta-cell leptin receptor is indicated by our observation that leptin (100 ng/ml) suppressed the secretion of insulin from islets isolated from ob/ob mice. Furthermore, leptin produced a marked lowering of [Ca2+]i in ob/ob beta-cells, which was accompanied by cellular hyperpolarization and increased membrane conductance. Cell-attached patch measurements of ob/ob beta-cells demonstrated that leptin activated ATP-sensitive potassium channels (K(ATP)) by increasing the open channel probability, while exerting no effect on mean open time. These effects were reversed by the sulfonylurea tolbutamide, a specific inhibitor of K(ATP). Taken together, these observations indicate an important physiological role for leptin as an inhibitor of insulin secretion and lead us to propose that the failure of leptin to inhibit insulin secretion from the beta-cells of ob/ob and db/db mice may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to NIDDM.
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PMID:Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. 916 85

A reduction of postprandial thermogenesis has been described in obesity; insulin resistance and/or decreased sympathetic nervous system activity seem to play the major role in its pathogenesis. On the other hand, a normal energy expenditure during exercise has been reported. At present, the response and the role of catecholamines in energy metabolism during exercise in obesity have not been well clarified yet. The aim of this work was to study the metabolic and hormonal changes caused by intense exercise in obesity. Nine obese subjects and ten normal weight controls were submitted to exhaustive exercise on a cycloergometer. Blood glucose, free fatty acids (FFA), glycerol, lactate, beta-OH-butyrate, insulin, glucagon, plasma growth hormone (HGH), catecholamine plasma levels were assayed before and at the end of exercise, and after a recovery period. The energy cost of exercise was evaluated by indirect calorimetry. In our experiment muscular exercise did not provoke any change in blood glucose and FFA plasma levels in either of our groups. In the obese subjects the insulin plasma levels were higher than in the controls. Glucagon plasma levels did not change. The exercise responses of norepinephrine (NE) (4.28 +/- 0.74 vs 8.81 +/- 1.35 nmol/l; P < 0.01), epinephrine (E) (234.21 +/- 64.18 vs 560.51 +/- 83.38 pmol/l; P < 0.01) and plasma growth hormone (HGH) (134.84 +/- 58.97 vs 825.92 +/- 195.25 pmol/l; P < 0.01) were significantly lower in obese subjects. At the end of exercise, the thermic effect of exercise did not differ between obese and control subjects (0.335 +/- 0.038 vs 0.425 +/- 0.040 kJ/min x kg fat-free mass. Our findings indicate that an impaired counterregulatory hormone response to exercise exists in obese subjects. The thermic effect of exercise does not seem to be affected by either the reduced catecholamine response nor insulin resistance.
Acta Diabetol 1997 Aug
PMID:Impaired counterregulatory hormonal and metabolic response to exhaustive exercise in obese subjects. 932 66

Leptin, the protein encoded by the obese (ob) gene, is secreted from adipose tissue and is thought to act in the central nervous system to regulate food intake and body weight. It has been proposed that leptin acts in the hypothalamus, the main control centre for satiety and energy expenditure. Mutations in leptin or the receptor isoform (Ob-R[L]) present in hypothalamic neurons result in profound obesity and symptoms of non-insulin-dependent diabetes. Here we show that leptin hyperpolarizes glucose-receptive hypothalamic neurons of lean Sprague-Dawley and Zucker rats, but is ineffective on neurons of obese Zucker (fa/fa) rats. This hyperpolarization is due to the activation of a potassium current, and is not easily recovered on removal of leptin, but is reversed by applying the sulphonylurea, tolbutamide. Single-channel recordings demonstrate that leptin activates an ATP-sensitive potassium (K[ATP]) channel. Our data indicate that the K(ATP) channel may function as the molecular end-point of the pathway following leptin activation of the Ob-R(L) receptor in hypothalamic neurons.
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PMID:Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. 939 3

As implemented in their program MINMOD, some of the parameters and variables of the equations representing Bergman and coworkers' minimal model of glucose metabolism have no simple rational relationship with the kinetic constants and constants of proportionality of the minimal model as such. In this work we implemented the original version of the minimal model, which does not suffer from this problem, and used it to investigate the source of insulin resistance among obese but otherwise healthy subjects. A fasting sampled intravenous glucose tolerance (FSIGT) test was performed in 38 healthy subjects of varying degrees of obesity (standard FSIGT test in 21 and tolbutamide FSIGT test in 17 subjects) in order to compare MINMOD and 'modified' equations (MI). Insulin sensitivity index (SI) in obese subjects was significantly lower than in lean subjects (4.58 +/- 3.5 vs. 11.7 +/- 4.3. 10(-5) min-1 (pmol.l-1)-1, P < 0.0001). The lower SI in obese subjects was a consequence P3 parameter (0.178 +/- 0.08 vs. 0.440 +/- 0.26.10(-5) min-2 (pmol.l-1)-1, P < 0.01), being p2 similar between obese and lean subjects (0.389 +/- 0.19 vs. 0.376 +/- 0.19.10(-1) min-1, NS). SI index correlated with p3 (r = 0.73, P < 0.0001), but not with p2 (r = 0.01, NS). Using these results and assuming that interstitial insulin is higher in obese subjects than in lean subjects, we have demonstrated that the proportionality constants of the model (k4 and k6) were lower in obese subjects than in lean subjects, but not the rate constant for insulin transfer across capillaries, k2. Our results suggest that the modified equations are a better theoretical approach to the minimal model method; and that low insulin sensitivity in obese subjects is due to receptor and/or post-receptor events rather than to slow transfer of insulin across capillary endothelium into the interstitial space.
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PMID:Minimal model of glucose metabolism: modified equations and its application in the study of insulin sensitivity in obese subjects. 959 83

1. Using whole-cell and cell-attached recording configurations, the effects of insulin on leptin activation of ATP-sensitive K+ (KATP) channels were examined in the CRI-G1 insulinoma cell line. 2. Whole-cell recordings demonstrated that the leptin-induced hyperpolarization and increased potassium conductance are completely occluded by prior exposure to insulin (1-50 nM). In cell-attached recordings, insulin prevented leptin activation of tolbutamide-sensitive KATP channels. Furthermore, insulin (50 nM) slowly and completely reversed the effects of leptin (10 nM), an action not attributable to direct inhibition of KATP channels per se. 3. Low concentrations of insulin-like growth factor-1 (IGF-1; 10-100 nM) failed to prevent leptin activation of KATP channels, although higher concentrations (1 microM) did inhibit leptin actions. 4. The action of insulin was specific for leptin, as the hyperglycaemic agent diazoxide activated KATP channels following prior exposure to insulin. 5. Wortmannin (1-10 nM) and LY 294002 (10 microM) prevented leptin activation of KATP channels, indicating an involvement of phosphoinositide 3-kinase (PI 3-kinase). 6. In conclusion, leptin activation of KATP channels is counter-regulated by insulin in the CRI-G1 insulinoma cell line. This feedback mechanism may be important in the local integration of hormonal signals which regulate insulin secretion and in alterations of metabolic homeostasis associated with obesity and non-insulin dependent diabetes mellitus (NIDDM).
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PMID:Insulin occludes leptin activation of ATP-sensitive K+ channels in rat CRI-G1 insulin secreting cells. 971 53

Obesity is often accompanied by non-insulin-dependent diabetes mellitus (type 2), arterial hypertension, and hyperlipidaemia. The aim of this study was to evaluate whether duration of obesity is a risk factor for the appearance of type 2 diabetes, hypertension, and hyperlipidaemia. We studied 760 obese subjects, 207 of whom had normal glucose tolerance, 125 impaired glucose tolerance, and 428 type 2 diabetes; in addition, 560 had hypertension and 315 had hyperlipidaemia. At univariate analysis, passing from normal through impaired glucose tolerance to type 2 diabetes there was a progressive increase of age and of duration of obesity, hypertension and hyperlipidaemia. Compared to subjects without hypertension, hypertensive subjects were older, had a longer duration of obesity, a greater body mass index (BMI, kg/m2), and more frequently a family history of hypertension; they also more frequently showed impaired glucose tolerance and type 2 diabetes and hyperlipidaemia. Compared to subjects without hyperlipidaemia, hyperlipidaemic subjects were older, had a longer duration of obesity, and more frequently showed impaired glucose tolerance and type 2 diabetes, and hypertension. Diabetes, hypertension, and hyperlipidaemia were highly associated, as up to 80% of subjects with type 2 diabetes had hypertension, and more than 80% of hyperlipidaemic subjects had hypertension. Type 2 diabetes was less frequent than hypertension and hyperlipidaemia during the first 10 years of obesity, and progressively increased thereafter; in contrast the frequency of hypertension and of hyperlipidaemia increased only after 30 years of obesity. In 359 subjects undergoing an oral glucose tolerance test (168 with simultaneous determination of insulin release), increasing durations of obesity were accompanied by an increasing prevalence of type 2 diabetes, and in deterioration of glucose response, with no decrease in insulin release. At logistic regression analysis, age was a common risk factor for diabetes, hypertension, and hyperlipidaemia; duration of obesity and hyperlipidaemia were additional risk factors for diabetes; family history of hypertension, BMI and hyperlipidaemia were additional risk factors for hypertension, as were impaired glucose tolerance or diabetes, and hypertension for hyperlipidaemia. These data indicate that duration of obesity is a risk factor for type 2 diabetes, and emphasize the importance of preventing obesity in young subjects.
Acta Diabetol 1998 Oct
PMID:Duration of obesity is a risk factor for non-insulin-dependent diabetes mellitus, not for arterial hypertension or for hyperlipidaemia. 984 Apr 48

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