Florencia Halperin1, Teresa Mezza2, Ping Li3, Jun Shirakawa4, Rohit N Kulkarni5, Allison B Goldfine6. 1. Joslin Diabetes Center, Boston, MA, United States of America; Brigham and Women's Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America. 2. Joslin Diabetes Center, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America; Endocrinologia e Diabetologia, Fondazione Policlinico Universitario A. Gemelli IRCSS, Roma, Italy; Università Cattolica del Sacro Cuore, Roma, Italy. 3. Joslin Diabetes Center, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America; Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, PR China. 4. Joslin Diabetes Center, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America; Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, Japan. 5. Joslin Diabetes Center, Boston, MA, United States of America; Brigham and Women's Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America. Electronic address: rohit.kulkarni@joslin.harvard.edu. 6. Joslin Diabetes Center, Boston, MA, United States of America; Brigham and Women's Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America. Electronic address: agoldfine@bwh.harvard.edu.
Abstract
AIMS: Insulin potentiates glucose-stimulated insulin secretion. These effects are attenuated in beta cell-specific insulin receptor knockout mice and insulin resistant humans. This investigation examines whether short duration insulin exposure regulates beta cell responsiveness to arginine, a non-glucose secretagogue, in healthy humans. MATERIALS AND METHODS: Arginine-stimulated insulin secretion was studied in 10 healthy humans. In each subject arginine was administered as a bolus followed by continuous infusion on two occasions one month apart, after sham/saline or hyperinsulinemic-isoglycemic clamp, respectively providing low and high insulin pre-exposure conditions. Arginine-stimulated insulin secretion was measured by C-peptide deconvolution, and by a selective immunogenic (DAKO) assay for direct measurement of endogenous but not exogenous insulin. RESULTS: Pre-exposure to exogenous insulin augmented arginine-stimulated insulin secretion. The effect was seen acutely following arginine bolus (endogenous DAKO insulin incremental AUC240-255min 311.6 ± 208.1 (post-insulin exposure) versus 120.6 ± 42.2 μU/ml•min (sham/saline) (t-test P = 0.021)), as well as in response to continuous arginine infusion (DAKO insulin incremental AUC260-290min 1095.3 ± 592.1 (sham/saline) versus 564.8 ± 207.1 μU/ml•min (high insulin)(P = 0.009)). Findings were similar when beta cell response was assessed using C-peptide, insulin secretion rates by deconvolution, and the C-peptide to glucose ratio. CONCLUSIONS: We demonstrate a physiologic role of insulin in regulation of the beta cell secretory response to arginine.
AIMS: Insulin potentiates glucose-stimulated insulin secretion. These effects are attenuated in beta cell-specific insulin receptor knockout mice and insulin resistant humans. This investigation examines whether short duration insulin exposure regulates beta cell responsiveness to arginine, a non-glucose secretagogue, in healthy humans. MATERIALS AND METHODS: Arginine-stimulated insulin secretion was studied in 10 healthy humans. In each subject arginine was administered as a bolus followed by continuous infusion on two occasions one month apart, after sham/saline or hyperinsulinemic-isoglycemic clamp, respectively providing low and high insulin pre-exposure conditions. Arginine-stimulated insulin secretion was measured by C-peptide deconvolution, and by a selective immunogenic (DAKO) assay for direct measurement of endogenous but not exogenous insulin. RESULTS: Pre-exposure to exogenous insulin augmented arginine-stimulated insulin secretion. The effect was seen acutely following arginine bolus (endogenous DAKO insulin incremental AUC240-255min 311.6 ± 208.1 (post-insulin exposure) versus 120.6 ± 42.2 μU/ml•min (sham/saline) (t-test P = 0.021)), as well as in response to continuous arginine infusion (DAKO insulin incremental AUC260-290min 1095.3 ± 592.1 (sham/saline) versus 564.8 ± 207.1 μU/ml•min (high insulin)(P = 0.009)). Findings were similar when beta cell response was assessed using C-peptide, insulin secretion rates by deconvolution, and the C-peptide to glucose ratio. CONCLUSIONS: We demonstrate a physiologic role of insulin in regulation of the beta cell secretory response to arginine.
Authors: Chirag Jain; Fataneh Fathi Far; Sarah Homberg; Katharina Wißmiller; Felizitas Gräfin von Hahn; Aurelia Raducanu; Silvia Schirge; Michael Sterr; Sara Bilekova; Johanna Siehler; Julius Wiener; Lena Oppenländer; Amir Morshedi; Aimée Bastidas-Ponce; Gustav Collden; Martin Irmler; Johannes Beckers; Annette Feuchtinger; Michal Grzybek; Christin Ahlbrecht; Regina Feederle; Oliver Plettenburg; Timo D Müller; Matthias Meier; Matthias H Tschöp; Ünal Coskun; Heiko Lickert Journal: Nature Date: 2021-01-27 Impact factor: 49.962
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