Glucose Stimulates Pulsatile Insulin Secretion from Human Pancreatic Islets by Increasing Secretory Burst Mass: Dose-Response Relationships
Abstract
Insulin is secreted almost exclusively in discrete bursts, and physiological regulation is accomplished by modulation of the pulse mass. How the integrity of contiguous anatomic structures in the human pancreas (islets, splanchnic innervation, exocrine tissue, local hormones) directs the coordinated insulin secretion is not known. We posed the hypothesis that glucose stimulates insulin secretion from isolated human islets by an amplification of insulin pulse mass with no change in pulse frequency and that the glucose dose-response curve for the regulation of insulin pulse mass mirrors that recognized in vivo. Islets from five nondiabetic cadaveric donors were perifused in a recently validated perifusion system at 4 mM and subsequently at 8, 12, 16, or 24 mM glucose. The effluent was collected in 1-min intervals and used for the measurement of insulin (ELISA). Pulsatile insulin secretion was analyzed by deconvolution analysis. Total insulin secretion increased progressively (P < 0.0001). This augmentation was due to amplified pulse mass (3-fold, 24 mM vs. 4 mM glucose; P < 0.0001) with no change in pulse interval (approximately 4 min). Pulsatile insulin secretion was stimulated most effectively in a physiologic concentration range of 4-8 mM. The islet insulin content was significantly correlated to the magnitude of first and second phase insulin secretion (P < 0.0001). The quantifiable orderliness of pulsatile insulin secretion rose with escalating glucose concentration (P = 0.02). In conclusion, glucose stimulates pulsatile insulin secretion from isolated human islets by amplification of insulin pulse mass without altering pulse interval. The in vitro concentration-response relationship is comparable with that observed in vivo. These data imply that transplanted human islets should be able to reproduce glucose-regulated insulin secretion as observed in the intact human pancreas.
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- Authors
- Ritzel, R. A., Veldhuis, J. D., & Butler, P. C.
- Affiliations
- University of Southern California (US)
- Mayo Clinic (US)
- Corresponding author
- Butler, Peter C.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2003-02
- Volume
- 88
- Issue
- 2
- Pages
- 742-747
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2100133653
- Cited by
- 56
- References
- 43
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 2
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061539, DK 61539)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- pulsatile insulin secretion, human pancreatic islets, islet perifusion, islet transplantation, glucose-stimulated insulin secretion
- MeSH terms
- Insulin Secretion, Adult, Cells, Cultured, Dose-Response Relationship, Drug, Female, Glucose, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Perfusion, Pulsatile Flow, Islets of Langerhans Transplantation, In Vitro Techniques
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