Hypothesis: Role of Reduced Hepatic Insulin Clearance in the Pathogenesis of Type 2 Diabetes
- 14 August 2019
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 68 (9), 1709-1716
- https://doi.org/10.2337/db19-0098
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.Keywords
Funding Information
- National Institute of Diabetes and Digestive and Kidney Diseases (DK27619, DK29867)
- Janssen Research and Development
This publication has 53 references indexed in Scilit:
- Insulin resistance in the nervous systemTrends in Endocrinology & Metabolism, 2012
- The CEACAM1 expression is decreased in the liver of severely obese patients with or without diabetesDiagnostic Pathology, 2011
- Age‐Related Changes in Insulin Sensitivity and β‐Cell Function Among European‐American and African‐American WomenObesity, 2011
- The genetics of type 2 diabetes: what have we learned from GWAS?Annals of the New York Academy of Sciences, 2010
- Disposition Index, Glucose Effectiveness, and Conversion to Type 2 DiabetesDiabetes Care, 2010
- Minimal model assessment of hepatic insulin extraction during an oral test from standard insulin kinetic parametersAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- β-Cell “rest” accompanies reduced first-pass hepatic insulin extraction in the insulin-resistant, fat-fed canine modelAmerican Journal of Physiology-Endocrinology and Metabolism, 2007
- CEACAM1 regulates insulin clearance in liverNature Genetics, 2002
- Transendothelial insulin transport is not saturable in vivo. No evidence for a receptor-mediated process.JCI Insight, 1996
- Mechanisms for hyperglycemia in type II diabetes mellitus: Therapeutic implications for sulfonylurea treatment—an updateThe American Journal of Medicine, 1991