INTERPLAY OF NUTRIENTS AND HORMONES IN THE REGULATION OF GLUCAGON-RELEASE

INTERPLAY OF NUTRIENTS AND HORMONES IN THE REGULATION OF GLUCAGON-RELEASE
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DOI:
10.1210/endo-117-3-817
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发表时间:
1985-01-01
期刊:
影响因子:
4.8
通讯作者:
VANDEWINKEL, M
VANDEWINKEL, M
中科院分区:
医学2区
文献类型:
--
作者:
PIPELEERS, DG;SCHUIT, FC;VANDEWINKEL, M

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通过自体荧光激活细胞分选纯化的胰腺A[α]细胞,研究了营养物质和激素在调节胰升糖素释放中的作用。纯化的A细胞在1.4 mM葡萄糖中孵育1小时后缺乏分泌活性。它们的释放机制可以被精氨酸、丙氨酸和谷氨酰胺单独或联合激活。葡萄糖通过对胰腺A细胞的不依赖于胰岛素的直接作用抑制氨基酸诱导的胰升糖素释放。营养诱导的胰高血糖素释放被生长抑素抑制,被(Bu)2cAMP或肾上腺素放大。10-11M生长抑素抑制肾上腺素刺激,10-10M抑制肾上腺素刺激。生长抑素和肾上腺素的作用与细胞内cAMP水平的平行变化有关,而氨基酸或葡萄糖引起的变化则不是这样。钙是释放胰高血糖素的基本要求。与其对生长抑素的高度敏感性不同,高血糖素的释放过程对胰岛素相对不敏感--在1小时的暴露中。这种激素只影响肾上腺素诱导的胰高血糖素释放,其抑制作用是部分的,仅在10-7M观察到。胰岛素的抑制作用不是由于葡萄糖处理的变化,而是与肾上腺素的刺激作用有关。营养诱导的信号与激素诱导的cAMP信号相互作用,激活胰腺A细胞的分泌过程。
The role of nutrients and hormones in the regulation of glucagon release is investigated in pancreatic A [alpha] cells purified by autofluorescence-activated cell sorting. Purified A cells lack secretory activity in 1-h incubations at 1.4 mM glucose. Their release mechanism can be activated by arginine, alanine, and glutamine, alone or in combination. Glucose inhibits amino acid-induced glucagon release through a direct insulin-independent action upon pancreatic A cells. Nutrient-induced glucagon release is suppressed by somatostatin and amplified by (Bu)2cAMP or epinephrine. The epinephrine stimulus is inhibited by 10-11 M somatostatin and abolished by 10-10 M of this peptide. The effects of somatostatin and epinephrine are associated with parallel changes in cellular cAMP levels, which is not the case for the variations induced by amino acids or glucose. Calcium is an essential requirement for glucagon release. In contrast to its exquisite sensitivity for somatostatin, the glucagon release process is relatively insensitive to insulin-during a 1-h exposure. The hormone affects solely epinephrine-induced glucagon release and its inhibitory action is partial and only observed at 10-7 M. This suppressive effect of insulin is not attributable to variations in glucose handling but appears associated with the stimulatory effect of epinephrine. A nutrient-induced signal interacts with a hormone-inducible cAMP signal to activate the secretory process in pancreatic A cells.