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OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the β3 adrenergic receptor (β3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4 ± 2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or β3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of β3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203 ± 50.3 vs 462.2 ± 83.6 ms²; mean ± s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with β3AR polymorphism in decreasing sympathetic nervous system activity. [ABSTRACT FROM AUTHOR]

We designed the present study to clarify whether the development of nephropathy was accelerated by a combination of hypertension and non-insulin-dependent diabetes. Spontaneously hypertensive rats with non-insulin-dependent diabetes induced by neonatal streptozotocin treatment (25.0-75.0 mg/kg) were separated into severely or mildly diabetic groups according to their non-fasting plasma glucose levels at 12 weeks of age and the findings were compared with the data on a control group treated with citrate buffer alone. The natural courses of urinary excretion rate of total protein, the molecular composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis with laser desitometer and N-acetyl-β-D-glucosaminidase were measured in the three groups from 12 weeks until 36 weeks of age. Total urinary protein in the control group decreased with age ( p<0.05), while in the mildly diabetic group changes were nil; in the severely diabetic group, however, the excretion rates of total urinary protein and high molecular weight protein consistently and progressively increased with age ( p<0.05). The low molecular weight protein continuously decreased with age in the mildly diabetic and control groups ( p<0.05), while in the severely diabetic group there was no decrease after 28 weeks of age. The urinary N-acetyl-β-D-glucosaminidase markedly increased ( p<0.05) in the severely diabetic group throughout the period compared with findings in the control group, but drastically decreased ( p<0.05) in the mildly diabetic group with age. There were significant correlations between the mean glycosylated haemoglobin levels and all the urinary parameters measured ( p<0.05). These observations suggest that development of nephropathy is accelerated by the glycaemic level in hypertensive rats. This new model should be appropriate for studying the combined effects of hypertension and diabetes mellitus on the kidney. [ABSTRACT FROM AUTHOR]

This study was designed to develop an animal model of Type 2 (non-insulin-dependent) diabetes with persistent hypertension. Male spontaneously hypertensive rats were treated with 25.0, 37.5, 50.0, 62.5 or 75.0 mg/kg of streptozotocin given intraperitoneally at 2 days of age and maintained for 12 weeks. In the rats which received 50.0 mg/kg or more streptozotocin, overt hyperglycaemia gradually and consistently developed following incomplete recovery from an initial hyperglycaemia. Compared to vehicle-treated controls, body weight gain in these animals did not differ for the first 8 weeks; thereafter, it was slightly but significantly ( p < 0.05) reduced. The animals treated with 25.0 or 37.5 mg/kg streptozotocin developed mild to moderate hyperglycaemia, but their body weight gain was similar to controls. The relationships between streptozotocin dose and metabolic responses (plasma glucose, glycosylated haemoglobin, urinary glucose, food intake, etc.) were clearly demonstrated. Systolic blood pressure rose with progressing age in both controls and streptozotocin-treated rats, irrespective of dosage or metabolic response. This new rat model of Type 2 diabetes associated with persistent hypertension may be useful in studying these combined effects on small and large vessels. [ABSTRACT FROM AUTHOR]