糖尿病における高ソマトスタチン血の成因に関する実験的研究
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It is generally presumed that somatostatin (immunoreactive somatostatin, IRS), which exists abundantly in pancreas and gastrointestinal tract, plays an important role on metabolism of nutrients. Many reports are currently available concerning the hypersecretion of IRS, and increase of pancreatic and gastric IRS contents in experimentally diabetic animals. In the present study, to investigate what mechanism account for the hypersomatostatinemia in diabetic animals, changes of portal plasma IRS levels were mesured in streptozotocin (40-50mg/kg B. W., STZ)-treated Wistar strain male rats and the effects of various treatments on portal plasma IRS levels were also examined. Portal plasma IRS levels increased at 4h after intravenous STZ inj2ction which being coincident with initial hyperglycemia. and decreased after 7h with severe hypoglycemia. After 24h and later, portal plasma· glucose was above 400mg/100ml. Whereas portal plasma IRS levels increased progressively from 106±13 (mean±SEM) at 24h to 641±115pg/ml at the 30th day. Decreases of portal plasma IRS levels caused by 24h- and 72h-fasting were greater in STZ-diabetic rats than in control rats, but IRS contents of pancreas increased at 24h- and 72h-fasting in STZ-diabetic rats. Intragastric glucose (3g/kg B. W.) resulted in a significant elevation of portal plasma IRS levels in control rats, whereas STZ-diabetic rats did not show any significant changes in portal plasma IRS levels. Furtermore, a single intravenous injection of insulin (10 U/kg B. W.) was not appreciable affected on portal plasma IRS levels in STZ-diabetic rats. On the other hand, daily insulin (8-12 U/day/rat) therapy caused the normalization of plasma glucose, polyphagia and body weight. Furthermore, basal portal plasma IRS levels weresignificantly failed by diet restriction and were normalized by daily insulin therapy in STZ-diabetic rats. Hyperresponse of portal plasma IRS for intravenous arginine(400mg/kg B. W.) injection was decreased by 24h-fasting and was normalized by daily insulin therapy and diet restriction in STZ-diabetic rats. Plasma glucose and free fatty acid increased after intravenous anti-insulin serum injection, but there were no significant changes in portal plasma IRS levels. These findings suggest that the genesis of hypersomatostatinemia in STZ-diabetic rats may be a consequence of total metabolic derangement caused by chronic insulin deficiency.
- 神戸大学の論文
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