Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat
Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat
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DOI：
10.1172/jci118727
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发表时间：
1996-06-15
影响因子：
15.9
通讯作者：
McGarry, JD
中科院分区：
文献类型：
--
作者：
Stein, DT;Esser, V;McGarry, JD
我们询问是否在离体大鼠胰腺制剂中观察到的众所周知的饥饿诱导的葡萄糖刺激的胰岛素分泌（GSIS）受损也适用于体内。因此，对进食和禁食18-24小时的大鼠进行静脉内葡萄糖激发，然后进行高血糖钳夹方案，在此期间测量血浆胰岛素浓度。令人惊讶的是，两组中的急性（5分钟）胰岛素反应同样稳健。然而，在输注抗脂解剂烟酸以确保葡萄糖负荷前血浆FFA的低水平后，禁食大鼠的GSIS基本消融，但进食动物未受影响。烟酸处理大鼠（进食或禁食）联合给予Intraperoid+肝素维持高血浆FFA浓度，或非烟酸处理禁食动物输注依托莫西（阻断肝脂肪酸氧化）进一步升高内源性FFA水平，导致GSIS超正常。体内研究结果在用来自进食和禁食大鼠的灌注胰腺进行的研究中重现，其中在不存在和存在棕榈酸盐的情况下检查GSIS。结果确定，在大鼠中，伴随食物剥夺的高循环FFA浓度是禁食终止时有效GSIS的必要条件。它们还有助于强调葡萄糖和脂肪酸在正常β细胞功能中的强大相互作用，并提高体内两种燃料之间的不平衡可能产生病理后果的可能性。
We asked whether the well known starvation-induced impairment of glucose-stimulated insulin secretion (GSIS) seen in isolated rat pancreas preparations also applies in vivo. Accordingly, fed and 18-24-h-fasted rats were subjected to an intravenous glucose challenge followed by a hyperglycemic clamp protocol, during which the plasma-insulin concentration was measured, Surprisingly, the acute (5 min) insulin response was equally robust in the two groups, However, after infusion of the antilipolytic agent, nicotinic acid, to ensure low levels of plasma FFA before the glucose load, GSIS was essentially ablated in fasted rats, but unaffected in fed animals,Maintenance of a high plasma FFA concentration by coadministration of Intralipid plus heparin to nicotinic acid-treated rats (fed or fasted), or further elevation of the endogenous FFA level in nonnicotinic acid-treated fasted animals by infusion of etomoxir (to block hepatic fatty acid oxidation), resulted in supranormal GSIS. The in vivo findings were reproduced in studies with the perfused pancreas from fed and fasted rats in which GSIS was examined in the absence and presence of palmitate, The results establish that in the rat, the high circulating concentration of FFA that accompanies food deprivation is a sine qua non for efficient GSIS when a fast is terminated. They also serve to underscore the powerful interaction between glucose and fatty acids in normal beta cell function and raise the possibility that imbalances between the two fuels in vivo could have pathological consequences.