Piccinini F, Polidori D, Gower B, Bergman R

African Americans (AA) tend to have higher plasma insulin concentrations than European Americans (EA); the increased insulin concentrations have been attributed to increased secretion and/or decreased insulin clearance by liver or other tissues. This work aims to characterize the contributions of hepatic versus extra-hepatic insulin degradation related to ethnic differences between AA versus EA. Using a recently-developed mathematical model employing insulin and C-peptide measurements from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT), we estimated hepatic vs. extra-hepatic insulin clearance in 29 EA and 18 AA healthy women. During the first 20 min of the FSIGT, plasma insulin was approximately twice as high in AA vs. EA. In contrast, insulin was similar in AA versus EA following the 20-25 min IV insulin infusion. Hepatic insulin first-pass extraction was 2/3 lower in AA vs. EA in the overnight fasted state. In contrast, extra-hepatic insulin clearance was not lower in AA compared to EA. The difference in insulin degradation between AA and EA can be attributed totally to liver clearance. The mechanism underlying reduced insulin degradation in AA remains to be clarified, as does the relative importance of reduced liver clearance to increased risk for type 2 diabetes mellitus.

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