Hitoshi Nishioka

Reduced noradrenaline turnover in streptozotocin-induced diabetic rats

SummaryTo clarify whether activity of the sympathetic nervous system is decreased in streptozotocin-induced diabetic rats, noradrenaline turnover, which is a reliable indicator of sympathetic nervous system activity, was measured in the interscapular brown adipose tissue, heart and pancreas of streptozotocin diabetic rats. Results from studies using inhibition of noradrenaline biosynthesis with α-methyl-p-tyrosine demonstrated significant reductions (p<0.05-0.001) in sympathetic nervous system activity in the interscapular brown adipose tissue, heart and pancreas of streptozotocin (65 mg/kg) diabetic rats, compared with measurements in streptozotocin (35 mg/kg) diabetic and saline-control rats. The daily injections of neutral protamine Hagedorn insulin to streptoz/otocin (65 mg/kg) diabetic rats prevented the decrease of noradrenaline turnover in the interscapular brown adipose tissue and heart significantly (p<0.02), but this was less marked in pancreas, compared with non-treated streptozotocin (65 mg/kg) diabetic rats. Furthermore reduced noradrenaline turnover was also observed in the control rats which showed comparable changes in body weight to the rats injected with streptozotocin (65 mg/kg). These results suggest that poorly controlled streptozotocin diabetic rats may have reduced sympathetic nervous function, and that insulin therapy might prevent this.

Reduced norepinephrine turnover in mice with monosodium glutamate-induced obesity

The disappearance of norepinephrine from the heart, interscapular brown adipose tissue (BAT), and pancreas has been examined in mice with monosodium glutamate (MSG)-induced obesity and in untreated controls. MSG-treated mice became obese in the absence of increased food intake and their core temperature was significantly lower compared to control mice. The rate of norepinephrine turnover following blockade of norepinephrine synthesis with alpha-methyl-para-tyrosine was significantly slower in heart and interscapular BAT of these mice than in untreated controls, but MSG had no effect on the pancreas. It is suggested that reduced norepinephrine turnover may be a major factor in the development of obesity after neonatal administration of MSG.

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).

Reduced norepinephrine turnover in brown adipose tissue of pre-obese mice treated with monosodium-L-glutamate

Norepinephrine (NE) turnover, an index of sympathetic nervous system (SNS) activity, was measured in interscapular brown adipose tissue (IBAT), heart and pancreas of 3-weeks-old pre-obese monosodium-L-glutamate (MSG) mice and at 6-weeks-old mildly obese MSG mice. In IBAT, rates of NE turnover were slower not only in 3-weeks-old MSG mice but also in older obese MSG mice than in their saline controls. In heart, rates of NE turnover were slower in 6-weeks-old mildly obese MSG mice, but not in pre-obese MSG mice. No significant difference in NE turnover in pancreas was observed at either age. The low NE turnover in IBAT of MSG-treated mice prior to the onset of gross obesity suggests that low SNS activity may be an initial contributor to their high energy efficiency and resultant obesity.

Glucose intolerance in chronic renal failure

慢性腎不全に耐糖能異常が存在することはよく知られているが, その成因については不明な点が少なくない. インスリン抵抗性もその一因と考えられているが, この点をさらに明らかにするためにインスリン受容体の面から検討した. 未透析腎不全患者10名, 透析患者12名および正常者6名を対象に赤血球のインスリン受容体を検討し, 0.5g/kgのIVGTTを行い, K値 (血糖消失率) およびΣIRI (IRIの総和) を求めた. K値は未透析群 (1.32±0.30) では正常群 (1.92±0.25), 透析群 (1.82±0.34) と比べて低値を示したが, 正常群と透析群との間には差がなかった. ΣIRIは未透析群 (445±78μU/ml), 透析群 (420±80μU/ml) は正常群 (260±38μU/ml) と比べて高値を示したが, 未透析群と透析群との間には差がなかった. インスリン特異結合率 (赤血球2.4×109個/mlへの0.2ng/mlの125I-インスリン) は未透析群 (3.99±0.76%) は低値を示したが, 正常群 (5.50±0.69%) と透析群 (5.11±0.80%) との間には有意差がなかった. Scatchard解析より, 未透析群におけるインスリン特異結合率の低下はインスリン受容体数の減少によるものと思われた (正常群64個/cell; 透析群58個/cell; 未透析群45個/cell).さらに, 耐糖能異常とインスリン受容体との関係を明らかにするために, インスリン特異結合率とK値および空腹時IRI, ΣIRIとの関係をみたが, 透析群において特異結合率とK値との間に正の相関を認めた. このことより, 未透析腎不全患者の耐糖能異常はインスリン受容体数の低下によるものと思われ, 透析療法はインスリン受容体レベルでの改善により耐糖能障害を正常化させるものと思われた.