Journal
METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 128, Issue -, Pages -Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2021.155117
Keywords
Arginine; Beta cell regulation; Insulin resistance; Insulin secretion
Categories
Funding
- American Diabetes Association [06-CD-07]
- National Institutes of Health [R01 DK070648, R01 DK067536]
- Joslin Diabetes and Research Center (DRC) [P30 DK036836]
- National Natural Science Foundation of China [81170779]
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This study investigates the regulatory role of insulin in the beta cell response to arginine stimulation in healthy humans. The results demonstrate that pre-exposure to insulin enhances arginine-stimulated insulin secretion. This finding reveals the physiological role of insulin in regulating beta cell response to non-glucose secretagogues.
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 dura-tion 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 AUC(240-255min) 311.6 +/- 208.1 (post-insulin exposure) versus 120.6 +/- 42.2 mu U/ml.min (sham/saline) (t-test P = 0.021)), as well as in response to continuous arginine infusion (DAKO insulin incremental AUC(260-290min) 1095.3 +/- 592.1 (sham/saline) versus 564.8 +/- 207.1 mu U/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. (c) 2022 Elsevier Inc. All rights reserved.
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