Gakuji Nomura

Variation of the Fatty Acid Binding Protein 2 Gene Is Not Associated With Obesity and Insulin Resistance in Japanese Subjects

An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects.

Phenotypic characterization of the β3-adrenergic receptor mutation and the uncoupling protein 1 polymorphism in Japanese men

The Trp64Arg mutation of the beta3-adrenergic receptor (beta3AR) gene and A to G polymorphism of the uncoupling protein 1 (UCP1) gene are reported to be associated with weight gain, and both have been shown to have an additive effect on weight gain in Caucasians. Racial differences have also been noted in the beta3AR mutation; however, the effect of UCP1 polymorphism on body weight is not obvious in the Japanese. Thus, we investigated the association of genetic variations in beta3AR and UCP1 genes and the additive effects of these two genes in 214 Japanese men. The frequency of the Trp64Arg allele was 0.19, and serum triglyceride was significantly higher in Arg64 homozygotes versus Trp64 homozygotes. The frequency of the G allele was 0.51, and the body mass index (BMI) was significantly higher in subjects with the G allele (GG homozygotes and AG heterozygotes) versus those without it (AA homozygotes). The beta3AR mutation and UCP1 polymorphism were not found to have additive effects, and they were not related to glucose tolerance patterns and insulin resistance. Our results suggest that the beta3AR mutation is associated with hypertriglyceridemia and the UCP1 polymorphism may be a weak contributing factor to obesity in Japanese men.

Essential hypertension and multiple renal arteries

Abstract Two hundred forty-three consecutive renal arteriograms were studied. Thirty-seven of 110 cases of essential hypertension (31 per cent) and 9 of 41 normotensive cases (22 per cent) revealed multiple renal arteries, showing that there is no significant difference in the incidence of multiple renal arteries between the two groups. Renal function study by intravenous pyelography, renogram, and angiography showed no difference between essential hypertension with multiple renal arteries and that with single renal artery. Plasma renin activity in peripheral and renal venous blood also showed neither increase nor difference in both kidneys, suggesting no significant ischemic changes in the kidney with multiple renal arteries. The general cause of hypertension observed in multiple renal arteries also cannot be related to renal anomaly or dysplasia itself. We conclude that multiple renal arteries are not an etiological factor in essential hypertension.

Effect of Propranolol on Sodium Reabsorption and the Renal Circulation

The effects of intrarenal arterial (6.5 µ g/kg/min) and intravenous (33 µ g/kg/min) administration of propranolol on sodium excretion and renal hemodynamics were st

Intrarenal Blood Flow in Essential Hypertension

Intrarenal blood flow was measured by the 133Xe washout method in 22 patients with essential hypertension. Mean RBF, the percentage of flow in component I, and fraction of renal mass supplied by component I were significantly reduced in patients with proteinuria, severe nephrosclerosis, cardiomegaly, and retinal changes of Keith-Wagener III and IV. Flow rate in component I was also reduced in the patients with severe nephrosclerosis, retinal changes of Keith-Wagener III and IV, and proteinuria. We conclude that redistribution of intrarenal blood flow occurs in essential hypertension with renal, cardiac, and retinal complications.

Distribution of Intrarenal Blood Flow after Renal Denervation in the Dog

The effect of acute denervation of the kidney on renal sodium and water excretion, and hemodynamics including intrarenal blood flow, was studied in anesthetized dogs. The intrarenal blood flow was measured by the radioactive microsphere method. In all experiments denervation natriuresis and diuresis was observed without significant change in glomerular filtration rate, renal blood flow and distribution of intrarenal blood flow. There was, however, an associated increase in potassium excretion. We suggest that denervation natriuresis and diuresis may be caused by the elimination of a direct nervous control of sodium and water reabsorption.

S20G mutation of the amylin gene in Japanese patients with type 2 diabetes.

Amylin is a major protein component of islet amyloid, and thought to be a pancreatic islet hormone that plays a role similar to insulin and glucagon in the maintenance of glucose homeostasis [1]. Recently, Sakagashira et al. [2] reported that a serine to glycine missense mutation at position 20 of the amylin molecule (S20G) was found in 4.1% of Japanese patients with type 2 diabetes and 10% of those with early-onset type 2 diabetes, whereas the mutation was not found in non-diabetic subjects and type 1 diabetic patients. Racial differences have been noted in the frequency and role of the S20G mutation in association with the development of diabetes. No mutation was found in Caucasians [3–5]. The mutation was found in Chinese and Taiwanese subjects, but an association with diabetes was only established among the former [6,7]. In contrast to the findings of Sakagashira et al., Yamada et al. [8] reported that the frequency of the mutation was not statistically different between Japanese type 2 diabetic patients and subjects with normal glucose tolerance (NGT). To help clarify this apparent inconsistency in the role of the S20G mutation in the development of diabetes in Japanese subjects, we investigated the mutation in 308 Japanese patients with type 2 diabetes aged from 20 to 89 years (60.9912.2 years, mean9SD), and 149 NGT subjects with no family histories of diabetes aged from 40 to 67 years (50.996.3 years, mean9SD). Type 2 diabetes and NGT were defined by the World Health Organization (WHO) criteria. In the type 2 diabetic patients (a total of 175 men and 133 women), 150 subjects had family histories of dia* Corresponding author. Tel.: +81-76-2652234; fax: +8176-2344250.