Klaff L J, Dunning B E, Taborsky G J
Department of Medicine, Pacific Medical Center, Seattle, Washington 98144.
Endocrinology. 1988 Dec;123(6):2668-74. doi: 10.1210/endo-123-6-2668.
Somatostatin-28 (S-28) is a naturally occurring N-terminally extended form of the tetradecapeptide somatostatin (S-14). The concept has arisen that S-28 is a gut hormone that regulates insulin secretion. This concept is based on 1) reports that S-28 is a more potent inhibitor of insulin secretion than S-14; 2) the finding that S-28 is present in D-cells of the intestine and is released after a meal; and 3) the demonstration of selective binding of S-28 to B-cells of the rat islet. To critically test this hypothesis we have 1) measured the circulating levels of somatostatin-like immunoreactivity (SLI) during infusions of S-28 and S-14 to accurately compare their potencies to inhibit insulin and glucagon secretion from the in vivo dog pancreas, and 2) measured the circulating levels of endogenous SLI released after a meal and compared these to the circulating levels of infused S-28 needed to inhibit insulin secretion. Infusion of S-28 at rates of 170 and 500 pmol/min raised arterial SLI levels by 282 +/- 26 and 885 +/- 98 fmol/ml, respectively. Immunoreactive insulin (IRI) output was inhibited by 20 +/- 11% (P less than 0.05) and 52 +/- 7% (P less than 0.0005), respectively. Immunoreactive glucagon (IRG) output was not significantly altered by either dose. Pancreatic SLI output was inhibited by 32 +/- 5% (P less than 0.0005) by the 500 pmol/min infusion. Infusion of S-28 at 50 pmol/min increased arterial SLI by 108 +/- 17 fmol/ml, but did not alter IRI output (+4 +/- 20%). In comparison, infusion of S-14 (100 pmol/min) raised arterial SLI levels by a similar amount (110 +/- 21 fmol/ml), but, unlike S-28, inhibited both IRI (-50 +/- 6%, P less than 0.0005) and IRG output (-17 +/- 8%; P less than 0.05). Thus, comparable increments in arterial S-28 failed to reproduce the inhibition of IRI secretion seen during the S-14 infusion, while similar inhibition was seen with an 8-fold increment. This suggests that S-28 is significantly less potent than S-14 in the dog. After a mixed meal, endogenous SLI levels increased by 35 +/- 3 fmol/ml in arterial plasma.(ABSTRACT TRUNCATED AT 400 WORDS)
生长抑素 - 28（S - 28）是天然存在的十四肽生长抑素（S - 14）N端延伸形式。有观点认为S - 28是一种调节胰岛素分泌的肠激素。这一观点基于以下几点：1）有报道称S - 28比S - 14对胰岛素分泌的抑制作用更强；2）发现S - 28存在于肠道的D细胞中且进食后释放；3）已证实S - 28能选择性结合大鼠胰岛的B细胞。为严格验证这一假说，我们进行了以下操作：1）在输注S - 28和S - 14过程中测量生长抑素样免疫反应性（SLI）的循环水平，以准确比较它们抑制体内犬胰腺胰岛素和胰高血糖素分泌的效力；2）测量进食后内源性SLI的循环水平，并将其与抑制胰岛素分泌所需的输注S - 28的循环水平进行比较。以170和500 pmol/min的速率输注S - 28，分别使动脉SLI水平升高282±26和885±98 fmol/ml。免疫反应性胰岛素（IRI）分泌分别被抑制20±11%（P＜0.05）和52±7%（P＜0.0005）。两种剂量的S - 28均未显著改变免疫反应性胰高血糖素（IRG）的分泌。以500 pmol/min的速率输注S - 28时，胰腺SLI分泌被抑制32±5%（P＜0.0005）。以50 pmol/min的速率输注S - 28使动脉SLI升高108±17 fmol/ml，但未改变IRI分泌（+4±20%）。相比之下，输注S - 14（100 pmol/min）使动脉SLI水平升高相似幅度（110±21 fmol/ml），但与S - 28不同的是，它同时抑制了IRI（-50±6%，P＜0.0005）和IRG分泌（-17±8%；P＜0.05）。因此，动脉S - 28的可比增量未能重现S - 14输注期间所见的IRI分泌抑制，而8倍增量时则出现了类似的抑制。这表明在犬体内，S - 28的效力明显低于S - 14。进食混合餐之后，动脉血浆中内源性SLI水平升高了35±3 fmol/ml。（摘要截短于400字）
