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假说：肝胰岛素清除率降低在 2 型糖尿病发病机制中的作用。

Hypothesis: Role of Reduced Hepatic Insulin Clearance in the Pathogenesis of Type 2 Diabetes.

机构信息

Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA

Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.

出版信息

Diabetes. 2019 Sep;68(9):1709-1716. doi: 10.2337/db19-0098.

DOI:10.2337/db19-0098
PMID:31431441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6702636/
Abstract

There is wide variance among individuals in the fraction of insulin cleared by the liver (20% to 80%). Hepatic insulin clearance is 67% lower in African Americans than European Americans. Clearance is also lower in African American children 7-13 years of age. Lower hepatic insulin clearance will result in peripheral hyperinsulinemia: this exacerbates insulin resistance, which stresses the β-cells, possibly resulting in their ultimate failure and onset of type 2 diabetes. We hypothesize that lower insulin clearance can be a primary cause of type 2 diabetes in at-risk individuals.

摘要

个体肝脏清除的胰岛素比例（20% 至 80%）差异很大。非裔美国人的肝胰岛素清除率比欧洲裔美国人低 67%。7-13 岁的非裔美国儿童的清除率也较低。较低的肝胰岛素清除率将导致外周高胰岛素血症：这会加剧胰岛素抵抗，从而对β细胞造成压力，可能导致其最终衰竭并引发 2 型糖尿病。我们假设较低的胰岛素清除率可能是高危个体 2 型糖尿病的主要原因。

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本文引用的文献

[1]
Dissection of hepatic versus extra-hepatic insulin clearance: Ethnic differences in childhood.

Diabetes Obes Metab. 2018-8-20

[2]
Quantitative path to deep phenotyping: Possible importance of reduced hepatic insulin degradation to type 2 diabetes mellitus pathogenesis.

J Diabetes. 2018-7-2

[3]
Variability of Directly Measured First-Pass Hepatic Insulin Extraction and Its Association With Insulin Sensitivity and Plasma Insulin.

Diabetes. 2018-5-11

[4]
Assessment of hepatic insulin extraction from in vivo surrogate methods of insulin clearance measurement.

Am J Physiol Endocrinol Metab. 2018-3-6

[5]
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.

Lancet Diabetes Endocrinol. 2018-3-5

[6]
Hepatic but Not Extrahepatic Insulin Clearance Is Lower in African American Than in European American Women.

Diabetes. 2017-10

[7]
Direct Hepatocyte Insulin Signaling Is Required for Lipogenesis but Is Dispensable for the Suppression of Glucose Production.

Cell Metab. 2016-6-14

[8]
Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data.

Diabetes. 2016-6

[9]
CB1R antagonist increases hepatic insulin clearance in fat-fed dogs likely via upregulation of liver adiponectin receptors.

Am J Physiol Endocrinol Metab. 2015-10-15

[10]
Elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation during diet-induced insulin resistance in dogs.

Diabetologia. 2015-11

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