The DOI matches its Crossref record; 136 of the 136 references it cites were found in a registry or an index.
Regulation of Insulin Secretion in Human Pancreatic Islets
Abstract
Pancreatic β cells secrete insulin, the body's only hormone capable of lowering plasma glucose levels. Impaired or insufficient insulin secretion results in diabetes mellitus. The β cell is electrically excitable; in response to an elevation of glucose, it depolarizes and starts generating action potentials. The electrophysiology of mouse β cells and the cell's role in insulin secretion have been extensively investigated. More recently, similar studies have been performed on human β cells. These studies have revealed numerous and important differences between human and rodent β cells. Here we discuss the properties of human pancreatic β cells: their glucose sensing, the ion channel complement underlying glucose-induced electrical activity that culminates in exocytotic release of insulin, the cellular control of exocytosis, and the modulation of insulin secretion by circulating hormones and locally released neurotransmitters. Finally, we consider the pathophysiology of insulin secretion and the interactions between genetics and environmental factors that may explain the current diabetes epidemic.
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In the citing paper
“The primary secretory pathway of glucose-stimulated insulin secretion is associated with complex patterns of electrical activity across the plasma membrane, which allow Ca2+ ions to enter the cell and trigger the secretory machinery.”
From Mathematical Modelling of Endocrine Systems (2019) · cites this paper as [11]
In the citing paper
“This electrical activity is coupled to cell metabolism, which acts as a glucose sensor by raising the intracellular ATP:ADP ratio, causing KATP channels to close, depolarising the membrane and driving it towards its threshold for action potential initiation [11].”
From Mathematical Modelling of Endocrine Systems (2019) · cites this paper as [11]
In the citing paper
“Adrenaline and somatostatin lead to transient repolarization and suppression of glucose-induced electrical activity (327, 568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“The action potentials of human β-cells are also triggered from a more negative membrane potential in human than in mouse β-cells (-60 mV rather than -50 to -40 mV) and often overshoot, peaking at potentials above zero mV (568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“The action potentials of both mouse and human β-cells are short, ranging between 5 ms (human) and 30-40 ms (mouse) (568, 570).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“Thus, delayed rectifying K+ channels may not activate much during the human β-cell action potential, which lasts only ~5 ms (568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“Blocking SK channels with apamin, or the non-selective antagonist NS8593, results in membrane depolarization and action potential firing in human β-cells (311) and stimulates insulin secretion (568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“Inhibition of inward rectifiers with Ba2+ (0.1 mM) or Cs+ (1 mM) in human β-cells exposed to glucose (6 mM) and tolbutamide (0.1 mM) resulted in membrane depolarization and stimulation of action potential firing (568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“These currents were blocked by low concentrations of Ba2+ (100 μM) and Cs+ (1 mM).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“The Ba2+-sensitive current displayed strongly inward rectification and reversed at ~-85 mV, which is close to EK.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“In human β-cells, hyperpolarizing voltage steps from a holding potential of -70 mV evoked progressively larger tolbutamide-resistant inward currents (553, 568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“Similarly, in human β-cells exposed to 6 mM glucose, carbachol evoked membrane depolarization (~5 mV) and increased action potential firing (568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [568]
In the citing paper
“The smallest cell aggregates reported by the authors were ca. 200 microns in diameter; the typical human islet has a diameter of ca. 130 microns176.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [176]
Citations
Cites
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β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.1.102 · Cited by 4,011
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Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40
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The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
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Cited by
Sorted by citations
Zamponi, G. W., Striessnig, J., Koschak, A., & DOLPHIN, A. C. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009654 · Cited by 1,158
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793
Self-citationMolecular pathways associated with oxidative stress in diabetes mellitus
Ighodaro, O. M. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.09.058 · Cited by 585
Role of Insulin in Health and Disease: An Update
Rahman, M. S., Hossain, K. S., Das, S., Kundu, S., Adegoke, E. O., Rahman, M. A., Hannan, M. A., Uddin, M. J., & Pang, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126403 · Cited by 574
Exocytosis and Endocytosis: Modes, Functions, and Coupling Mechanisms
Wu, L., Hamid, E., Shin, W., & Chiang, H. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170305 · Cited by 462
Metadata
- Authors
- Rorsman, P., & Braun, M.
- Affiliations
- University of Oxford (GB)
- University of Alberta (CA)
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2013-02-10
- Volume
- 75
- Issue
- 1
- Pages
- 155-179
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2140402299
- Cited by
- 599
- References
- 134
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 26 · 2023: 44 · 2022: 60 · 2021: 57 · 2020: 42 · 2019: 41 · 2018: 59 · 2017: 47 · 2016: 50 · 2015: 51 · 2014: 54 · 2013: 28
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (095531/Z/11/Z, 095531)
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- insulin secretion, pancreatic beta cells, human beta cells, glucose detection, action potential, ion channels, exocytosis, neurotransmitters, circulating hormones, diabetes mellitus, genetic and environmental risk factors
- MeSH terms
- Insulin Secretion, Action Potentials, Diabetes Mellitus, Type 2, Glucose, Humans, Insulin, Ion Channels, Islets of Langerhans, Insulin-Secreting Cells
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