EFFECT OF HYPEROSMOLALITY ON BASAL AND HORMONE-STIMULATED HEPATIC GLUCOSE-METABOLISM INVITRO
EFFECT OF HYPEROSMOLALITY ON BASAL AND HORMONE-STIMULATED HEPATIC GLUCOSE-METABOLISM INVITRO
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DOI：
10.1111/j.1365-2362.1989.tb00206.x
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发表时间：
1989-04-01
影响因子：
5.5
通讯作者：
BRATUSCHMARRAIN, P
中科院分区：
文献类型：
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作者：
KOMJATI, M;KASTNER, G;BRATUSCHMARRAIN, P
为了更好地了解糖尿病患者在高渗状态下葡萄糖利用的损害，建立了体外模型来评估高渗对离体肝细胞基础葡萄糖摄取以及胰高血糖素依赖性葡萄糖释放的影响。在这些模拟高血糖（40 mmol葡萄糖）和高渗透压（高达500 mosm kg-1，NaCl作为添加溶质）状态的研究中，当渗透压增加低至10 mosm kg-1时，基础肝葡萄糖摄取可逆性抑制19%。当通过添加尿素或甘露醇来增加孵育液的渗透压时，对离体肝细胞的葡萄糖摄取没有这种影响。在400和300 mosmkg-1下对3-O-甲基葡萄糖的转运速率和2-脱氧葡萄糖的摄取的估计表明，由于摄取进一步降低，受损的细胞内酶活性而不是葡萄糖进入细胞的转运速率是导致高渗缺陷的原因2-脱氧葡萄糖的渗透压摩尔浓度（16%）比3-O-甲基葡萄糖（13%）增加（P < 0.025）。当用NaCl作为添加的溶质将重量摩尔渗透压浓度提高到400 mosm kg-1时，从分离的肝细胞释放的胰高血糖素依赖性葡萄糖减少了17%。这些体外获得的数据支持临床论点，即高渗状态（对应于液体丢失超过溶质）能够损害基础肝脏葡萄糖摄取以及糖原分解胰高血糖素对肝脏的作用。
To understand better impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the effects of hyperosmolality on abasal glucose uptake as well as glucagon dependent glucose release by isolated hepatocytes. In these studies simulating a hyperglycaemic (40 mmol glucose) and hyperosmolal (up to 500 mosm kg-1, NaCl as added solute) state basal hepatic glucose uptake was reversibly suppressed by 19% when osmolality was increased by as little as 10 mosm kg-1. No such effects on glucose uptake by isolated hepatocytes could be attained when the incubation''s fluid osmolality was augmented by the addition of urea or mannitol. Estimations of the transport rates of 3-O-methyl glucose and uptake of 2-deoxyglucose at 400 vs 300 mosm kg-1 revealed that impaired intracellular enzymatic activity but not the transport rate of glucose into the cell were responsible for the hyperosmolal defect as uptake was more reduced (P < 0.025) by increased osmolality for 2-deoxyglucose (16%) than for 3-O-methylglucose (13%). Glucagon dependent glucose release from isolated hepatocytes was diminished by 17.cntdot.8% when the osmolality was raised to 400 mosm kg-1 by NaCl as added solute. These data obtained in vitro support the clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal hepatic glucose uptake as well as glycogenolytic glucagon action on the liver.