MECHANISMS OF GLUCAGON-SECRETION DURING INSULIN-INDUCED HYPOGLYCEMIA IN MAN - ROLE OF THE BETA-CELL AND ARTERIAL HYPERINSULINEMIA
MECHANISMS OF GLUCAGON-SECRETION DURING INSULIN-INDUCED HYPOGLYCEMIA IN MAN - ROLE OF THE BETA-CELL AND ARTERIAL HYPERINSULINEMIA
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DOI：
10.1172/jci111315
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发表时间：
1984-01-01
影响因子：
15.9
通讯作者：
UNGER, RH
中科院分区：
文献类型：
--
作者：
BOLLI, G;DEFEO, P;UNGER, RH
研究了7例正常受试者和5例< 15个月的胰岛素依赖型糖尿病（IDDM）患者胰高血糖素对低血糖反应的调控机制，胰高血糖素是反调节激素反应的重要组成部分，以及胰岛内胰岛素的作用。持续时间)。在正常受试者中，低血糖(动脉血浆葡萄糖[PG] 53 +-。静脉滴注胰岛素（30 mU/m2 .cntdot）诱导3 mg/dl)。1 h和游离免疫反应性胰岛素[FIRI] 58 .+-。2 .mu。U/ml)引起胰岛素分泌下降100%，胰高血糖素升高7.5 ng/ml / 120min。当内源性胰岛素分泌受到抑制时。50或50英镑。85%通过高胰岛素-血糖钳夹（FIRI 63 .+-）。1.5或147 .+-。0.3 .mu。U/ml)低血糖前，α。细胞对低血糖的反应与对照研究相同。当simeq刺激内源性胰岛素分泌时。100%高胰岛素-高血糖钳夹，FIRI 145 +-。1.5 .mu。U/ml, PG 132 +-。2毫克/分升)低血糖前，α。细胞对低血糖的反应也与对照研究的反应重叠。在c肽阴性的糖尿病患者中，连续一夜静脉注射胰岛素使血糖达到正常水平。尽管缺乏β，但细胞对低血糖的反应与正常受试者相当。高胰岛素-正糖钳夹2小时，FIRI为61 .+-。2 .mu.U /毫升)。胰高血糖素对胰岛素诱导的低血糖的反应显然与正常人内源性胰岛内和外源性动脉胰岛素浓度的水平无关。与之前的报道相反，在缺乏内源性胰岛素分泌的情况下，这种反应可能是正常的。失去了。因此，细胞功能不负责。alpha。IDDM患者胰岛素诱导低血糖时细胞衰竭。
The mechanisms controlling the response of glucagon to hypoglycemia, a vital component of the counterregulatory hormonal response and the role of intraislet insulin were studied in 7 normal subjects and 5 subjects with insulin-dependent diabetes mellitus (IDDM) (of < 15-mo. duration). In the normal subjects, hypoglycemia (arterial plasma glucose [PG] 53 .+-. 3 mg/dl) was induced by an i.v. insulin infusion (30 mU/m2 .cntdot. min for 1 h and free immunoreactive insulin [FIRI] 58 .+-. 2 .mu.U/ml) elicited a 100% fall in insulin secretion and an integrated rise in glucagon of 7.5 ng/ml per 120 min. When endogenous insulin secretion was suppressed .simeq. 50 or .simeq. 85% by a hyperinsulinemic-euglycemic clamp (FIRI 63 .+-. 1.5 or 147 .+-. 0.3 .mu.U/ml, respectively) before hypoglycemia, the .alpha. cell responses to hypoglycemia were identical to those of the control study. When the endogenous insulin secretion was stimulated by .simeq. 100% (hyperinsulinemic-hyperglycemic clamp, FIRI 145 .+-. 1.5 .mu.U/ml, PG 132 .+-. 2 mg/dl) before hypoglycemia, the .alpha. cell responses to the hypoglycemia were also superimposable on those of the control study. In C-peptide negative diabetic subjects made euglycemic by a continuous overnight i.v. insulin infusion, the .alpha. cell responses to hypoglycemia were comparable to those of normal subjects despite absent .beta. cell secretion and were not affected by antecedent hyperinsulinemia (hyperinsulinemic-euglycemic clamp for 2 h, FIRI 61 .+-. 2 .mu.U/ml). The glucagon response to insulin-induced hypoglycemia is evidently independent of the level of both endogenous intraislet and exogenous arterial insulin concentration in normal man. This response may be normal in the absence of endogenous insulin secretion, in contrast to earlier reports. Loss of .beta. cell function is therefore not responsible for .alpha. cell failure during insulin-induced hypoglycemia in IDDM.