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MO YIN CHAN, E. L. BRADLEY and W. N. HOLMES

SUMMARY

The distribution and disappearance of radioactivity after the intravenous administration of [1,2-3H]corticosterone and [1,2-3H]aldosterone to the pigeon were studied according to one- and two-compartment model systems. The volume of distribution (AVD) of the total and methylene chlorideextractable radioactivity in the plasma of hypophysectomized pigeons injected with labelled corticosterone was significantly increased. Also the biological half-life (T½) of each radioactive fraction in plasma was significantly prolonged. No significant change in the metabolic clearance rate (MCR) of labelled corticosterone was observed in the hypophysectomized pigeon.

The AVD of the total and methylene chloride-extractable tritium in the plasma of the hypophysectomized pigeon injected with labelled aldosterone was unchanged but the T½ of both plasma fractions was significantly prolonged. The estimated MCR of labelled aldosterone was significantly diminished.

The concentration of total fluorogenic corticosteroid in plasma from the chronically hypophysectomized pigeon was reduced to one-third of that in the sham-operated bird, and corticotrophin-replacement therapy restored the concentration to normal. After hypophysectomy, the plasma corticosterone concentration was reduced to 20% of the concentration in the sham-operated birds, and replacement therapy with corticotrophin again restored the plasma levels to normal. Estimation of the endogenous corticosterone secretory rates indicated that chronic hypophysectomy was accompanied by a decline commensurate with the reduction in the plasma corticosterone concentration.

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W Yin, D Liao, M Kusunoki, S Xi, K Tsutsumi, Z Wang, X Lian, T Koike, J Fan, Y Yang and C Tang

The synthetic compound NO-1886 (ibrolipim) is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides. Recently, we found that NO-1886 also reduced plasma free fatty acids and glucose in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 treatment on ectopic lipid deposition and the islet pathology in miniature swine fed a high-fat/high-sucrose diet. Our results showed that feeding this diet to miniature swine caused insulin resistance, increased lipid deposition in non-adipose tissue, such as in the heart, skeletal muscle, liver and pancreas, and also caused pancreatic beta cell damage. However, supplementing 1% NO-1886 (200 mg/kg per day) into the high-fat/high-sucrose diet decreased ectopic lipid deposition, improved insulin resistance, and alleviated the beta cell damage. These results suggest that improvement of lipid disorder, non-adipose tissue steatosis and insulin resistance may be very important for the protection of beta cell damage. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistance syndrome.