Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data
Autor: | David Polidori, Anne E. Sumner, Stephanie T. Chung, Richard N. Bergman |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Adult Blood Glucose Male medicine.medical_specialty Intravenous Glucose Tolerance Endocrinology Diabetes and Metabolism medicine.medical_treatment Black People 030209 endocrinology & metabolism Models Biological 03 medical and health sciences Insulin infusion chemistry.chemical_compound 0302 clinical medicine Insulin resistance Interquartile range Internal medicine Diabetes mellitus Internal Medicine medicine Humans Insulin Glucose tolerance test medicine.diagnostic_test C-Peptide C-peptide business.industry Fasting Glucose Tolerance Test medicine.disease 030104 developmental biology Endocrinology Metabolism Glucose chemistry Liver Injections Intravenous Female Insulin Resistance business |
Zdroj: | Diabetes |
ISSN: | 1939-327X 0012-1797 |
Popis: | Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin concentration 37 pmol/L) were used. Endogenous insulin secretion (calculated by C-peptide deconvolution) and insulin infusion rates were used as inputs to a new two-compartment model of insulin kinetics and hepatic and extrahepatic clearance parameters were estimated. Good agreement between modeled and measured plasma insulin profiles was observed (mean normalized root mean square error 6.8%), and considerable intersubject variability in parameters of insulin clearance among individuals was identified (the mean [interquartile range] for hepatic extraction was 25.8% [32.7%], and for extrahepatic insulin clearance was 20.7 mL/kg/min [11.7 mL/kg/min]). Parameters of insulin clearance were correlated with measures of insulin sensitivity and acute insulin response to glucose. The method described appears promising for future research aimed at characterizing variability in insulin clearance and the mechanisms involved in the regulation of insulin clearance. |
Databáze: | OpenAIRE |
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