Glucose‐stimulated insulin secretion: A newer perspective
Open accessAbstract
Existing concepts and models for glucose‐stimulated insulin secretion (GSIS) are overviewed and a newer perspective has been formulated toward the physiological understanding of GSIS. A conventional model has been created on the basis of in vitro data on application of a square wave high glucose in the absence of any other stimulatory inputs. Glucose elicits rapid insulin release through an adenosine triphosphate‐sensitive K+ channel (K ATP channel)‐dependent mechanism, which is gradually augmented in a K ATP channel‐independent manner. Biphasic GSIS thus occurs. In the body, the β‐cells are constantly exposed to stimulatory signals, such as glucagon‐like peptide 1 (GLP‐1), parasympathetic inputs, free fatty acid (FFA), amino acids and slightly suprathreshold levels of glucose, even at fasting. GLP‐1 increases cellular cyclic adenosine monophosphate, parasympathetic stimulation activates protein kinase C, and FFA, amino acids and glucose generate metabolic amplification factors. Plasma glucose concentration gradually rises postprandially under such tonic stimulation. We hypothesize that these stimulatory inputs together make the β‐cells responsive to glucose independently from its action on K ATP channels. Robust GSIS in patients with a loss of function mutation of the sulfonylurea receptor, a subunit of K ATP channels, is compatible with this hypothesis. Furthermore, pre‐exposure of the islets to an activator of protein kinase A and/or C makes β‐cells responsive to glucose in a K ATP channel‐ and Ca 2+‐independent manner. We hypothesize that GSIS occurs in islet β‐cells without glucose regulation of K ATP channels in vivo, for which priming with cyclic adenosine monophosphate, protein kinase C and non‐glucose nutrients are required. To understand the physiology of GSIS, comprehensive integration of accumulated knowledge is required.
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Insulin secretion from β-cells is stimulated by elevated exogenous glucose levels, such as those occurring after a meal.
“In contrast, insulin secretion from β-cells is stimulated by elevated exogenous glucose levels, such as those occurring after a meal.10”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [10]
In β-cells, the main stimulus for insulin release is elevated blood glucose levels following a meal.
“In β-cells, the main stimulus for insulin release are elevated blood glucose levels following a meal.10”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [10]
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- Authors
- Komatsu, M., Takei, M., Ishii, H., & Sato, Y.
- Affiliations
- Shinshu University (JP)
- Corresponding author
- Komatsu, Mitsuhisa
- Venue
- Journal of Diabetes Investigation
- Publisher
- Wiley
- Published
- 2013-05-15
- Volume
- 4
- Issue
- 6
- Pages
- 511-516
- ISSN
- 2040-1116 (ISSN-L)
- 2040-1124
- PMC
- PMC4020243
- OpenAlex
- W1989817905
- Cited by
- 256
- References
- 51
- Citations by year
- 2026: 6 · 2025: 25 · 2024: 25 · 2023: 27 · 2022: 29 · 2021: 26 · 2020: 26 · 2019: 17 · 2018: 23 · 2017: 14 · 2016: 13 · 2015: 18 · 2014: 7
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Diabetes Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21591128, 25461383)
- 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
- glucose-stimulated insulin secretion, pancreatic beta cells, ATP-sensitive potassium channels, sulfonylurea receptor, glucagon-like peptide-1, parasympathetic activation, free fatty acids, amino acids, cyclic AMP, protein kinase C, protein kinase A, biphasic insulin secretion, loss-of-function mutations, postprandial blood glucose
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