Insulin Sensitively Controls the Glucagon Response to Mild Hypoglycemia in the Dog

Author:

Igawa Kayano1,Mugavero Mike1,Shiota Masakazu1,Neal Doss W.1,Cherrington Alan D.1

Affiliation:

1. From the Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee

Abstract

In the present study, we examined how the arterial insulin level alters the α-cell response to a fall in plasma glucose in the conscious overnight fasted dog. Each study consisted of an equilibration (−140 to −40 min), a control (−40 to 0 min), and a test period (0 to 180 min), during which BAY R 3401 (10 mg/kg), a glycogen phosphorylase inhibitor, was administered orally to decrease glucose output in each of four groups (n = 5). In group 1, saline was infused. In group 2, insulin was infused peripherally (3.6 pmol · kg− 1 · min−1), and the arterial plasma glucose level was clamped to the level seen in group 1. In group 3, saline was infused, and euglycemia was maintained. In group 4, insulin (3.6 pmol · kg−1 · min−1) was given, and euglycemia was maintained by glucose infusion. In group 1, drug administration decreased the arterial plasma glucose level (mmol/l) from 5.8 ± 0.2 (basal) to 5.2 ± 0.3 and 4.4 ± 0.3 by 30 and 90 min, respectively (P < 0.01). Arterial plasma insulin levels (pmol/l) and the hepatic portal-arterial difference in plasma insulin (pmol/l) decreased (P < 0.01) from 78 ± 18 and 90 ± 24 to 24 ± 6 and 12 ± 6 over the first 30 min of the test period. The arterial glucagon levels (ng/l) and the hepatic portal-arterial difference in plasma glucagon (ng/l) rose from 43 ± 5 and 5 ± 2 to 51 ± 5 and 10 ± 5 by 30 min (P < 0.05) and to 79 ± 16 and 31 ± 15 (P < 0.05) by 90 min, respectively. In group 2, in response to insulin infusion, arterial insulin (pmol/l) was elevated from 48 ± 6 to 132 ± 6 to an average of 156 ± 6. The hepatic portal-arterial difference in plasma insulin was eliminated, indicating a complete inhibition of endogenous insulin release. The arterial glucagon level (ng/l) and the hepatic portal-arterial difference in plasma glucagon (ng/l) did not rise significantly (40 ± 5 and 7 ± 4 at basal, 44 ± 4 and 9 ± 4 at 90 min, and 44 ± 8 and 15 ± 7 at 180 min). In group 3, when euglycemia was maintained, the insulin and glucagon levels and the hepatic portal-arterial difference remained constant. In group 4, the arterial plasma glucose level remained basal (5.9 ± 1.1 mmol/l) throughout, whereas insulin infusion increased the arterial insulin level to an average of 138 ± 6 pmol/l. The hepatic portal-arterial difference in plasma insulin was again eliminated. Arterial glucagon level (ng/l) and the hepatic portal-arterial difference in plasma glucagon (ng/l) did not change significantly (43 ± 2 and 9 ± 2 at basal, 39 ± 3 and 9 ± 2 at 90 min, and 37 ± 3 and 7 ± 2 at 180 min). Thus, a difference of ∼120 pmol/l in arterial insulin completely abolished the response of the α-cell to mild hypoglycemia.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3