Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
Metab Syndr Relat Disord. 2005;3(1):51-9. doi: 10.1089/met.2005.3.51.
In the fed state, the glucose disposal action of insulin can be attributed in approximately equal part to the direct action of insulin and to a hepatic insulin sensitizing substance (HISS) that acts selectively on skeletal muscle. HISS action is absent in the 24-hour fasted state. The objective of this study was to determine whether alcohol administered with a meal affected meal-induced insulin sensitization (MIS).
Rats were fasted for 24 hours and anesthetized, and insulin sensitivity was evaluated using the rapid insulin sensitivity test (RIST). A liquid mixed meal was injected into the stomach along with diluted alcohol equivalent to 1, 0.25, and 0.125 mL/kg of ethanol. After 90 minutes, a second RIST was carried out, atropine administered, and a third RIST done. A control fed group received no ethanol and a RIST was determined at 90 minutes; then 1 mL/kg ethanol or water was administered and the RIST was tested 1 hour later.
Ethanol co-administered with a meal produced a dose-dependent suppression of MIS. MIS was blocked back to fasting levels by atropine. MIS developed to a maximal level by 90 minutes and was maintained for at least 1 hour more. Ethanol (1 mL/kg) administered after MIS was fully developed resulted in complete suppression of insulin sensitivity back to a fasting level.
MIS can be demonstrated in response to gastric administration of a liquid mixed meal in anesthetized rats. Alcohol produces a dose-related suppression of MIS and can completely reverse MIS once it has been developed. The concentrations of alcohol reached were well within levels attained by social drinkers. MIS was confirmed to act through HISS action, and neither MIS nor alcohol affected the HISS-independent component of insulin action.
在进食状态下，胰岛素的葡萄糖摄取作用可以归因于胰岛素的直接作用和选择性作用于骨骼肌的肝胰岛素敏感物质（HISS）的作用大致相等。在 24 小时禁食状态下，HISS 作用不存在。本研究的目的是确定在用餐时给予酒精是否会影响餐后胰岛素敏感性（MIS）。
大鼠禁食 24 小时并麻醉，使用快速胰岛素敏感性测试（RIST）评估胰岛素敏感性。将混合液餐注入胃中，并加入相当于 1、0.25 和 0.125 毫升/公斤乙醇的稀释酒精。90 分钟后，进行第二次 RIST，给予阿托品，然后进行第三次 RIST。对照组给予不含乙醇的饮食，并在 90 分钟时进行 RIST 测定；然后给予 1 毫升/公斤乙醇或水，并在 1 小时后进行 RIST 测试。
酒精与餐一起给药会产生剂量依赖性的 MIS 抑制。MIS 被阿托品阻断回空腹水平。MIS 在 90 分钟时达到最大水平，并至少维持 1 小时以上。在 MIS 完全发展后给予 1 毫升/公斤乙醇会导致胰岛素敏感性完全抑制回空腹水平。
在麻醉大鼠中，通过胃内给予混合液餐可以证明 MIS 的存在。酒精产生剂量相关的 MIS 抑制作用，并且一旦 MIS 发展，它可以完全逆转 MIS。达到的酒精浓度在社交饮酒者达到的水平范围内。MIS 被证实通过 HISS 作用起作用，并且 MIS 和酒精都不会影响胰岛素作用的 HISS 独立成分。
