Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of the relation between physical fitness and glucose homeostasis was evaluated in two studies: (A) a cross-sectional study on 108 middle-aged non-diabetic men; (B) a five-month training program involving nine males with non-insulin-dependent (type 2) diabetes. It was found that the level of physical fitness was positively related to glucose tolerance, and that this relation was largely independent of body weight and basal insulin secretion. Furthermore, the training program for the diabetics resulted in improved glucose tolerance without change in either body weight or glucose-induced insulin secretion. It is concluded that glucose balance is significantly influenced by the physical fitness level, which is likely to be an important element in the pathogenesis of type 2 diabetes as well as in the treatment of that disease.
Acta Diabetol Lat
PMID:Physical fitness, insulin secretion, and glucose tolerance in healthy males and mild type-2 diabetes. 634 26

Thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3) and HbA1c were assayed in 21 insulin-dependent (type 1) diabetics and in 45 non-insulin-dependent (type 2) diabetics with normal thyroid function and different levels of control, and were compared to values found in apparently healthy controls. rT3 and rT3/T3 ratio were significantly increased both in type 1 and type 2 diabetics. T3 and T4 were significantly lower in type 2 diabetics than in the controls. Significant positive correlations of HbA1c to rT3 (r = 0.63) and to rT3/T3 ratio (r = 0.53) were found in type 1, and in type 2 diabetics (HbA1c, rT3-r = 0.50), (HbA1c, rT3/T3-r = 0.37). There was no correlation between glycemia (BG), relative body weight (RBW) and thyroid hormones. These data suggest that the alterations of thyroid hormones in type 1 and type 2 diabetes mellitus reflect the degree of control better than the hyperglycemia and the duration of metabolic unbalance.
Acta Diabetol Lat
PMID:Correlation between different degree and duration of metabolic control and thyroid hormone levels in type 1 and type 2 diabetics. 666 5

The aim of the present paper was to evaluate the prevalence of the chlorpropamide-alcohol-flush (CPAF) in patients with type 2 and with type 1 diabetes. Ninety-seven patients with type 2 diabetes and 33 with type 1 diabetes drank 40 ml vermouth 12 h after placebo and again 12 h after 1 tablet of chlorpropamide (250 mg) or 12 h after the last of repeated administrations of chlorpropamide (250 mg b.i.d. for 2 days). Skin temperature was recorded in all patients by a thermocouple probe connected to the left cheek. In 47 patients serum concentrations of chlorpropamide and of its metabolite CBSU were also determined. The prevalence of CPAF was similar in type 1 and type 2 diabetes, was greater in women than in men, and was significantly greater after repeated administrations than after one single administration of chlorpropamide. The increase of skin temperature during a 30-min period was significantly higher in patients with CPAF than in patients without CPAF. Serum concentrations of chlorpropamide and of its metabolite CBSU were more elevated after 4 than after 1 tablet of chlorpropamide, but were not significantly different in patients with and without CPAF. These data indicate that both genetic factors and the amount of chlorpropamide used affect the appearance of CPAF. To assess the possible role of serotonin and of dopamine in the CPAF, some patients with CPAF were tested again after treatment with metergoline, an antiserotonin agent, or with bromocriptine, a dopamine-agonist. Neither drug influenced the CPAF, indicating that the two neurotransmitters are not involved in the CPAF.
Acta Diabetol Lat
PMID:Characterization of the chlorpropamide-alcohol-flush in patients with type 1 and type 2 diabetes. 688 May 63

Obese-hyperglycemic mice (genotype ob/ob) have hyperglycemia, hyperinsulinemia, increased resistance to insulin action and decreased insulin receptors on their liver, fat cell and muscle plasma membranes. Hypoglycemic sulfonylureas are reported to improve diabetic control by decreasing the insulin resistance of subjects with Type II diabetes mellitus: however, it is not clear if their mechanism is to increase plasma membrane insulin receptors or to decrease post-receptor insulin resistance. In this study we treated obese-hyperglycemic mice and their normal weight litter mates with the oral hypoglycemic sulfonylurea tolbutamide for 28 to 34 weeks. Tolbutamide administration to normal mice resulted in the following changes that were indicative of increased insulin action: (1) increased body weight; (2) increased epididymal fat-pad weight; (3) increased 2-deoxyglucose transport into the intact diaphragm muscle preparation. There was no alteration in plasma glucose, plasma insulin or pancreatic insulin content suggesting that the tolbutamide effect was an extrapancreatic effect that was probably not mediated by increased insulin secretion. There was no change in the insulin receptor number or affinity of liver cell membranes prepared from tolbutamide treated mice supporting the notion that the extrapancreatic effect of tolbutamide may occur at a post-insulin receptor location. In contrast to the normal mice, tolbutamide did not increase the body weight, epididymal fat pad weight, the already increased 2-deoxyglucose transport into diaphragm muscle or the decreased number of insulin receptors on hepatic plasma membranes. The tolbutamide caused a striking decrease in pancreatic insulin concentration and degranulation of the islets in obese but not normal mice. This is compatible with previous information that the obese mice have abnormal islets that are not under the normal feed-back control of ambient insulin concentration as are the islets of normal mice. We conclude that tolbutamide potentiates insulin action in normal, but not obese, mice and that this potentiation may be due to a post-insulin receptor action.
 ...
PMID:Effect of chronic tolbutamide administration on normal and obese-hyperglycemic mice: evidence for post-receptor potentiation of insulin action. 704 79

In a double-blind cross-over trial we compared the effects of placebo and propranolol on iv tolbutamide and oral glipizide-stimulated insulin secretion in 10 non-insulin dependent diabetics. The patients were randomly allocated for 2 weeks treatment with placebo and propranolol 80 mg twice daily. At the end of each period an iv tolbutamide test and an oral glipizide-glucose-test were performed. Tolbutamide-stimulated insulin secretion was not affected by propranolol. There was no change in blood glucose levels during the iv tolbutamide test (IVTT), which excluded an effect of blood glucose on insulin secretion. During the oral glipizide-glucose challenge propranolol decreased blood glucose at 60 min (P less than 0.01) and increased C-peptide at 0 min (P less than 0.01) and 30 min (P less than 0.05) compared with placebo. In contrast to earlier results obtained in animals and healthy subjects propranolol does not inhibit insulin- or C-peptide responses to sulphonylurea in patients with non-insulin dependent diabetes mellitus.
 ...
PMID:Propranolol does not inhibit sulphonylurea-stimulated insulin secretion in patients with non-insulin dependent diabetes mellitus. 705 22

The therapeutic effect of tolbutamide (1.5 g daily) in a random sample of patients with non-insulin dependent diabetes mellitus (NIDDM), was studied in a controlled, double-blind cross-over trial of 13 women and 6 men, aged 40-65 years and of 85-155% ideal body weight. The trial comprised C-peptide determinations during a standard carbohydrate rich meal followed by four periods of 3 months in which alternating tolbutamide and placebo were given. From the beginning to the end of the treatment periods fasting blood glucose was reduced from 11.9 +/- 1.1 (mean +/- SEM) to 10.0 +/- 0.8 mmol/l (P less than 0.025), glycohaemoglobin from 12.8% +/- 0.7 to 11.3% +/- 0.5 (P less than 0.02) with a close correlation between fasting blood glucose and glycohaemoglobin (r = 0.87, P less than 0.001). The observations during the first 3 months of study was not included in the calculations. Fasting C-peptide and fasting insulin concentrations were not significantly altered by tolbutamide treatment. The effect of tolbutamide was inversely correlated to the C-peptide response to the standard test meal at the start of the trial (r = 0.76, P less than 0.01), so that patients with the most pronounced beta-cell failure had the greatest therapeutical effect. The beta-cell response to the test meal could not identify patients, whose fasting blood glucose would be normalized by tolbutamide treatment.
 ...
PMID:Therapeutic effect of tolbutamide in non-insulin dependent diabetes mellitus (NIDDM). Relation to beta-cell function. 705 23

Genetic linkage studies of families with early-onset type 2 diabetes have facilitated the identification of diabetes-susceptibility genes. In order to assess the feasibility of using linkage approaches to identify genes responsible for the development of type 2 diabetes in Japanese subjects, we examined our clinical records for multigenerational families suitable for genetic studies. We identified 16 families in which at least one subject was diagnosed with type 2 diabetes before 25 years of age. Seven of these families had a pattern of inheritance consistent with a diagnosis of maturity-onset diabetes of the young (MODY) and nine families showed a complex pattern of inheritance of type 2 diabetes with transmission of diabetes-susceptibility genes from both parents. The glucokinase and mitochondrial tRNA(Leu(UUR)) genes were screened for mutations in at least one affected subject from each family in order to assess the contribution of mutations in these genes to the development of the diabetes. No mutations were found, which suggests that the diabetes in these families resulted from mutations in other genes.
Acta Diabetol 1995 Mar
PMID:Characterization of Japanese families with early-onset type 2 (non-insulin dependent) diabetes mellitus and screening for mutations in the glucokinase and mitochondrial tRNA(Leu(UUR)) genes. 754 40

Diastolic dysfunction may be the earliest marker of a diabetes-induced heart muscle disease which leads to the progressive development of cardiac failure. Left ventricular diastolic function was indirectly assessed using pulsed wave Doppler ultrasound mitral-flow velocities in 20 normotensive patients with a new diagnosis of type 2 diabetes mellitus, normal cardiac function and no evidence of coronary artery disease and in 16 age-matched normal subjects. Peak velocities of early (E) and late (A) left ventricular filling were measured. The median (interquartile ranges) peak E/A ratio was significantly reduced in the diabetic group 0.96 (0.8-1.2) vs 1.2 (1.1-1.3), P < 0.01. Despite improvements in glycaemic control over 3 months, HbA1c 9.9% (7.6%-10.5%) to 7.4% (6.5%-7.9%), P < 0.001, maintained at 6 months, HbA1c 7.0% (6.4%-7.3%), there were no changes in the E/A ratio, 0.96 (0.83-1.15) and 0.95 (0.83-1.17), respectively. Furthermore, there was no correlation between percentage change in HbA1c and E/A ratio over 6 months. The results of this study suggest that in patients with type 2 diabetes mellitus and normal systolic function, diastolic function was impaired at diagnosis and was not affected by an improvement in the glycaemic control.
Acta Diabetol 1995 Jun
PMID:Diastolic dysfunction is not related to changes in glycaemic control over 6 months in type 2 (non-insulin-dependent) diabetes mellitus. A cross-sectional study. 757 31

Recent data suggest that in a proportion of NIDDM patients there is a slowly evolving insulitis which results in a latent autoimmune diabetes leading to full insulin-dependence. Many animal models exist of NIDDM but none have reported the spontaneous existence of a similar phenomenon. We have re-examined the histology of pancreata from a few Psammomys obesus who had become insulin-dependent in the late stages of NIDDM. We report here the unexpected finding of the presence of insulitis in these animals and suggest that they could be a model for the clinical observation of latent IDDM in NIDDM patients.
Acta Diabetol 1995 Jun
PMID:Latent autoimmune diabetes mellitus in adult humans with non-insulin-dependent diabetes: is Psammomys obesus a suitable animal model? 757 41

The sulfonylureas are a class of oral hypoglycemic agents used to treat type II diabetes mellitus, and tolbutamide is a "first generation" member of this family. It is a nonpolar, weakly acidic drug that binds to serum albumin in the circulation. In the present study, we have examined the interactions of tolbutamide with human serum albumin by isothermal titration calorimetry and heteronuclear multiple-quantum coherence NMR spectroscopy. Calorimetric titrations revealed that tolbutamide binds to albumin at three independent sites with the same or comparable affinity. This result was independently confirmed by NMR experiments which resolved three resonances at 1H chemical shifts of 2.07, 2.11 and 2.14 ppm, corresponding to [methyl-13C]tolbutamide bound to three discrete binding sites. The binding affinity quantitated by calorimetry (Kd = 21 +/- 9 microM at pH 7.4, 37 degrees C) was approximately 5 times lower than the most frequently reported value. Tolbutamide titrations of albumin complexed with three other drugs whose binding sites have been localized by X-ray crystallography (salicylate, clofibric acid, and triiodobenzoic acid) demonstrated direct competition for common binding sites. NMR experiments with samples containing [methyl-13C]tolbutamide and these competing drugs permitted assignment of the resonances at 2.07 and 2.14 ppm to tolbutamide bound to the aspirin sites in albumin subdomains IIIA and IIA, respectively. These findings permit the first assignment of tolbutamide binding sites to specific locations on the albumin molecule within the context of the recently published crystal structure of human serum albumin. In addition, this information provides a molecular basis for predicting unfavorable drug interactions involving tolbutamide in patients with type II diabetes.
 ...
PMID:Localization of tolbutamide binding sites on human serum albumin using titration calorimetry and heteronuclear 2-D NMR. 761 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>