Keiji Yoshioka

Effects of caffeine on the uncoupling protein family in obese yellow KK mice.

1. The hypothesis that caffeine upregulates uncoupling protein (UCP)‐1, UCP‐2 and UCP‐3 expression, which contribute to thermogenesis, was investigated in obese mice.

Reduced norepinephrine turnover in interscapular brown adipose tissue of obese rats after ovariectomy

Norepinephrine (NE) turnover, which is a reliable indicator of sympathetic nervous system (SNS) activity, was measured in the interscapular brown adipose tissue (IBAT), heart, and pancreas of ovariectomized (OVX), sham-operated rats receiving injections of estradiol benzoate (EB). Ovariectomized rats (OVX rats) ate much more than controls and became obese, whereas the administration of EB to obese OVX rats decreased their food intake to the level below that of sham-operated animals and body weight to the level of sham controls. The results from studies using the inhibition of NE biosynthesis with alpha-methyl-p-tyrosine or radiolabeled NE to measure NE turnover significantly demonstrated reductions in SNS activity in IBAT of OVX rats than in sham controls, whereas the injections of EB to OVX rats significantly restored the decrease of NE turnover in IBAT. NE turnover in heart and pancreas were similar in these three groups. It is suggested that reduced NE turnover in IBAT may be a major factor in the development of obesity after ovariectomy (OVX).

The inter-arm difference in systolic blood pressure is a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.

Recent studies have suggested that the inter-arm blood pressure difference (IAD) is associated with cardiovascular events and mortality. The aim of this study was to assess whether the IAD could be a marker for subclinical atherosclerosis in patients with type 2 diabetes who are at high risk of cardiovascular disease (CVD). In a cross-sectional retrospective study of 206 Japanese patients with type 2 diabetes aged 49–76 years, we examined the correlation of the IAD with the carotid intima-media thickness (IMT), ankle-brachial index (ABI) or cardio ankle vascular index (CAVI). The IAD was positively correlated with the maximum IMT (r=0.266, P<0.0001), mean IMT (r=0.209, P=0.00726) or CAVI (r=0.240, P=0.0005). The IAD was higher in patients with CVD than in those without (P=0.0020). A multiple linear regression analysis demonstrated that the IAD was an independent determinant of maximum IMT (β=0.169, P=0.0167), mean IMT (β=0.178, P=0.0153), ABI (β=−0.222, P=0.0033) or CAVI (β=0.213, P=0.0011) after adjusting for known risk factors. The area under the receiver operating characteristic curve (AUC) of the IAD as a predictor of subclinical atherosclerosis was similar to the AUC of the Framingham 10-year coronary heart disease risk score. In conclusion, the IAD could be a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.

Genetic Variation in the β3-Adrenergic Receptor in Japanese NIDDM Patients

areas as well, including retroperitoneal and subcutaneous abdominal fat (3), and these properties may be the major determinants of the pathophysiological processes related to increased central adiposity, rather than site itself. CT and MRI are not considered ideal for larger scale investigations or routine screening because of costs, radiation, and availability. However, in small studies there is a weak relationship between anthropometric measures and intraabdominal fat, or insulin resistance, despite significant correlations between waist-to-hip ratio and cardiovascular morbidity and mortality in population studies (4). Using Dual Photon Xray Absorptiometry (DEXA, Lunar DPX-Lunar Radiation Corp., Madison, WI) for measurement of central abdominal fat, we found a strong correlation with hyperinsulinemic-euglycemic clamp-measured insulin sensitivity in women at both high and low risk of diabetes (5), as reported between CT-measured intra-abdominal fat and insulin sensitivity in young men (6). Correlation of insulin sensitivity with abdominal fat was significantly better than with other fat areas, including trunk and total fat (5). DEXA accurately assesses actual fat content of heterogeneous soft tissue and has been validated against other body fatness measures (7). DEXA abdominal fat measurement correlates well with assessment by CT, accounting for 80% of the variation in intra-abdominal fat by CT in postmenopausal women (8), and DEXAmeasured total abdominal fat does not differ significantly from CT (9). We use a window (Fig. 1) from upper L2 vertebra to lower L4 (where the ratio of subcutaneous fat to intra-abdominal fat is least) (10) drawn to exclude subcutaneous fat lateral to the inner costal margins (5). This window has good reproducibility (CV -5%) and excludes 3 0 % subcutaneous fat (crosschecked by MRI, D.G.C., L.V.C., D.J.C., unpublished data). The issue of which abdominal fat domain (if any) is the greatest contributor to the pathophysiological consequences of central adiposity remains unresolved. Further research will clarify the complex interactions of the bodys fat-containing tissues, which are proving to be much more than inert storage depots. Meanwhile, while not yet proposing it for routine clinical use, we recommend DEXA measurement of regional fat as a lowFigure 1—The DEXA areas of fat with the abdominal fat window as marked between 12 and IA and the inner costal margins. • , leg fat; H, arm fat; M, trunk fat; • , central abdominal fat.

Rapidly Progressive Glomerulonephritis due to Rifampicin Therapy

A 60-year-old man was treated with rifampicin, isoniazid, ethambutol and pyrazinamide for pulmonary tuberculosis. Acute renal failure developed 1 month after re-administration of rifampicin following 1 month’s interruption of treatment. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis. This is, to our knowledge, the fourth case of rapidly progressive crescentic glomerulonephritis associated with rifampicin treatment, which responded to methylprednisolone pulse therapy followed by oral steroid therapy.

Rapid Improvement of Serum 1,5-Anhydroglucitol Concentrations After Administration of α-Glucosidase Inhibitor

From the Epidemiology Unit (JFB.), Manitoba Health; the Departments of Medicine (S.L.) and Pediatrics (H.D.) and the Manitoba Centre for Health Policy and Evaluation (A.W), Department of Community Sciences, University of Manitoba; and the Diabetes Education Resource Program (K.A., N.D.), Winnipeg, Manitoba; and the Laboratory Centre for Disease Control (O.K.), Ottawa, Canada. Address correspondence to J. Blanchard, MD, Epidemiology Unit, Manitoba Health, 800 Portage Avenue, Room 405, Winnipeg, Manitoba R3G 0N4, Canada. E-mail: jamieb@mbnet.mb.ca.

Effect of ultrasonic stimulation on mRNA abundance of uncoupling protein (UCP) 2 and UCP 3 in gastrocnemius muscle of rats

1. The hypothesis that ultrasonic stimulation upregulates uncoupling protein (UCP) 2 and UCP3 in gastrocnemius muscle by a different mechanism of exercise was investigated in Wister rats.

Communications to the EditorPulmonary Administration of Insulin as an Aerosol

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Low carbohydrate intake and oral glucose-tolerance tests

observational study. With respect to the timing of treatment after unprotected intercourse, therefore, the WHO study should not automatically be accorded any more weight than the nine previous studies, despite its different result. Nevertheless, with the conflicting evidence, I agree with the conclusion that “women should receive treatment as soon as practicable after unprotected coitus”, provided that it is interpreted to mean that treatment could be delayed by a few hours to avoid having to take the second dose at a very inconvenient time (such as 0300 h) and provided that women are not denied treatment after 24 h, or after 48 h, or even after 72 h with proper informed consent, especially when the option of insertion of a copper intrauterine device is not available or appropriate.

Is Troglitazone a Real Indication for Obese Subjects With Impaired Glucose Tolerance

ations of parathyroid function should be investigated as a potential explanation for the associations between insulin and diabetes and bone mineral density An additional mechanism accounting for a reduction in bone formation is a direct effect of hyperglycemia on osteoblasts and their precursors. Advanced glycation end products (AGEs) have been found in the extracellular bone matrix in experimental studies. AGE-modified type I collagen has recently been demonstrated to inhibit osteoblastic function and may contribute to the reduced bone formation and, also by extension, to the reduction in bone turnover and activation frequency of bone remodeling (7). In fact, the trophic effect of insulin and various mechanisms reducing bone turnover may both contribute to the alterations of bone remodeling and the skeletal consequences of diabetes.