Related Experiment Video

Updated: Feb 7, 2026

Assessing Insulin Clearance in Mice via In Situ Liver Perfusion
07:30

Assessing Insulin Clearance in Mice via In Situ Liver Perfusion

Published on: December 13, 2024

814

Dissection of hepatic versus extra-hepatic insulin clearance: Ethnic differences in childhood

Francesca Piccinini1, David C Polidori2, Barbara A Gower3

  • 1Cedars-Sinai Medical Center, Diabetes and Obesity Research Institute, Los Angeles, California.

Diabetes, Obesity & Metabolism
|July 19, 2018
PubMed

Insights

African American children show lower hepatic insulin clearance than European American children, suggesting potential genetic factors contributing to metabolic disorders. This early difference in fractional hepatic insulin extraction (FEL) may impact insulin concentrations over time.

Area of Science:

  • Metabolic Health
  • Pediatric Endocrinology
  • Genetics and Epigenetics

Background:

  • Adult African American (AA) women exhibit significantly lower hepatic insulin clearance compared to European American (EA) women, leading to higher plasma insulin levels.
  • This disparity suggests potential underlying genetic or epigenetic factors influencing insulin metabolism from an early age.

Purpose of the Study:

  • To investigate whether impaired hepatic insulin clearance is present in African American (AA) children compared to European American (EA) and Hispanic American (HA) children.
  • To explore the potential role of genetic/epigenetic factors in early-life hepatic insulin clearance differences.

Main Methods:

  • A total of 203 children (ages 7-13) from AA, EA, and HA ethnic groups underwent a frequently sampled intravenous glucose tolerance test (FSIGT).
  • Glucose, insulin, and C-peptide levels were measured to calculate hepatic and extra-hepatic insulin clearances using mathematical modeling.

Main Results:

  • Fractional hepatic insulin extraction (FEL) was significantly lower in AA children (19%) compared to EA children (33%) (P = 0.0007).
  • These differences persisted after adjusting for age, Tanner stage, and body fat (P = 0.0012).
  • No significant differences in extra-hepatic insulin clearance were observed among the ethnic groups.

Conclusions:

  • Lower hepatic insulin extraction (FEL) in AA children at a young age supports the hypothesis that genetic/epigenetic factors may contribute to metabolic differences.
  • These early-life differences in hepatic insulin clearance could be linked to hyperinsulinemia and potentially predispose AA individuals to metabolic disorders later in life.
Abstract

Keywords:
insulin resistanceinsulin secretionliver

More Related Videos

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy07:10

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy

Published on: June 18, 2020

22.9K
Laparoscopic Anatomic S7+S8d Resection Preserving Inferior Right Hepatic Vein and S6 with Right Hepatic Vein Transection06:00

Laparoscopic Anatomic S7+S8d Resection Preserving Inferior Right Hepatic Vein and S6 with Right Hepatic Vein Transection

Published on: December 30, 2025

323

Related Concept Videos

Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance01:09

Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance

Hepatic clearance refers to the volume of blood cleared of a drug by the liver per unit of time. It plays a crucial role in drug metabolism and elimination. While hepatic clearance is commonly estimated by subtracting renal clearance from total body clearance, other pathways, such as pulmonary or biliary clearance, may also contribute. However, these pathways are generally less significant than hepatic and renal clearance.
Most drugs undergo restrictive clearance, which is proportional to the...
534
Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
311
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
565
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
301
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
281
Hepatic Portal System01:21

Hepatic Portal System

The hepatic portal system, a critical part of our circulatory framework, transports nutrient-laden, deoxygenated blood from the gastrointestinal tract and spleen to the liver. This ingenious system plays an indispensable role in maintaining our body's metabolic equilibrium.
At its core, the hepatic portal vein is the result of a confluence of the superior and inferior mesenteric veins along with the splenic vein. Each of these veins has a unique role. The superior mesenteric vein is...
6.0K