Insulin Reciprocally Regulates Glucagon Secretion in Humans

被引:100
作者
Cooperberg, Benjamin A. [1 ]
Cryer, Philip E. [1 ]
机构
[1] Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO 63130 USA
基金
美国国家卫生研究院;
关键词
INTRAISLET INSULIN; DIABETES-MELLITUS; AUTONOMIC FAILURE; ALPHA-CELLS; HYPOGLYCEMIA; RESPONSES; COUNTERREGULATION; DECREMENT; RELEASE; HYPERGLYCEMIA;
D O I
10.2337/db10-0728
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-We tested the hypothesis that an increase in insulin per se, i.e., in the absence of zinc, suppresses glucagon secretion during euglycemia and that a decrease in insulin per se stimulates glucagon secretion during hypoglycemia in humans. RESEARCH DESIGN AND METHODS We measured plasma glucagon concentrations in patients with type 1 diabetes infused with the zinc-free insulin glulisine on three occasions. Glulisine was infused with clamped euglycemia (similar to 95 mg/dl [5.3 mmol/l]) from 0 to 60 min on all three occasions. Then, glulisine was discontinued with clamped euglycemia or with clamped hypoglycemia (similar to 55 mg/dl [3.0 mmol/l]) or continued with clamped hypoglycemia from 60 to 180 min. RESULTS Plasma glucagon concentrations were suppressed by -13 +/- 3, -9 +/- 3, and -12 +/- 2 pg/ml (-3.7 +/- 0.9, -2.6 +/- 0.9, and -3.4 +/- 0.6 pmol/l), respectively, (all P < 0.01) during zinc-free hyperinsulinemic euglycemia over the first 60 min. Glucagon levels remained suppressed following a decrease in zinc-free insulin with euglycemia (-14 +/- 3 pg/ml [-4.0 +/- 0.9 pmol/l]) and during sustained hyperinsulinemia with hypoglycemia (-14 +/- 2 pg/ml [-4.0 +/- 0.6 pmol/l]) but increased to -3 +/- 3 pg/ml (-0.9 +/- 0.9 pmol/l) (P < 0.01) following a decrease in zinc-free insulin with hypoglycemia over the next 120 min. CONCLUSIONS These data indicate that an increase in insulin per se suppresses glucagon secretion and a decrease in insulin per se, in concert with a low glucose concentration, stimulates glucagon secretion. Thus, they document that insulin is a beta-cell secretory product that, in concert with glucose and among other signals, reciprocally regulates a-cell glucagon secretion in humans. Diabetes 59:2936-2940, 2010
引用
收藏
页码:2936 / 2940
页数:5
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