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Metformin Inhibits Mouse Islet Insulin Secretion and Alters Intracellular Calcium in a Concentration-Dependent and Duration-Dependent Manner near the Circulating Range
Joint Authors
Nunemaker, Craig S.
Gelin, Lindor
Li, Jiewen
Corbin, Kathryn L.
Jahan, Ishrat
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-03-18
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Metformin is considered the first-line treatment for type 2 diabetes.
While metformin primarily increases insulin sensitivity, evidence also suggests that metformin affects the activity of insulin-secreting pancreatic islets.
This study was designed to systematically examine the direct effects of metformin by measuring insulin secretion and the kinetics of the calcium response to glucose stimulation in isolated mouse islets using varying concentrations (20 μM, 200 μM, and 1 mM) and durations (~1, 2, and 3 days) of metformin exposure.
We observed both concentration- and duration-dependent inhibitory effects of metformin.
Concentrations as little as 20 μM (nearing circulating therapeutic levels) were sufficient to reduce insulin secretion following 3-day treatment.
Concentrations of 200 μM and 1 mM produced more pronounced effects more rapidly.
With 1 mM metformin, islets showed severe impairments in calcium handling, inhibition of insulin secretion, and increased cell death.
No stimulatory effects of metformin were observed for any experimental endpoint.
We conclude that the direct effects of metformin on islets are inhibitory at near-physiological concentrations.
Beneficial effects of metformin observed on islets under various stressors may occur by “resting” fatigued cellular processes.
However, metformin may have unintended consequences on normally functioning islets within the circulating range that require further evaluation.
American Psychological Association (APA)
Gelin, Lindor& Li, Jiewen& Corbin, Kathryn L.& Jahan, Ishrat& Nunemaker, Craig S.. 2018. Metformin Inhibits Mouse Islet Insulin Secretion and Alters Intracellular Calcium in a Concentration-Dependent and Duration-Dependent Manner near the Circulating Range. Journal of Diabetes Research،Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1184028
Modern Language Association (MLA)
Gelin, Lindor…[et al.]. Metformin Inhibits Mouse Islet Insulin Secretion and Alters Intracellular Calcium in a Concentration-Dependent and Duration-Dependent Manner near the Circulating Range. Journal of Diabetes Research No. 2018 (2018), pp.1-10.
https://search.emarefa.net/detail/BIM-1184028
American Medical Association (AMA)
Gelin, Lindor& Li, Jiewen& Corbin, Kathryn L.& Jahan, Ishrat& Nunemaker, Craig S.. Metformin Inhibits Mouse Islet Insulin Secretion and Alters Intracellular Calcium in a Concentration-Dependent and Duration-Dependent Manner near the Circulating Range. Journal of Diabetes Research. 2018. Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1184028
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1184028