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The cell biology of systemic insulin function
Open accessAbstract
Insulin is the paramount anabolic hormone, promoting carbon energy deposition in the body. Its synthesis, quality control, delivery, and action are exquisitely regulated by highly orchestrated intracellular mechanisms in different organs or “stations” of its bodily journey. In this Beyond the Cell review, we focus on these five stages of the journey of insulin through the body and the captivating cell biology that underlies the interaction of insulin with each organ. We first analyze insulin’s biosynthesis in and export from the β-cells of the pancreas. Next, we focus on its first pass and partial clearance in the liver with its temporality and periodicity linked to secretion. Continuing the journey, we briefly describe insulin’s action on the blood vasculature and its still-debated mechanisms of exit from the capillary beds. Once in the parenchymal interstitium of muscle and adipose tissue, insulin promotes glucose uptake into myofibers and adipocytes, and we elaborate on the intricate signaling and vesicle traffic mechanisms that underlie this fundamental function. Finally, we touch upon the renal degradation of insulin to end its action. Cellular discernment of insulin’s availability and action should prove critical to understanding its pivotal physiological functions and how their failure leads to diabetes.
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“An increase in circulating glucose levels is sensed by pancreatic β‐cells through the glucose transporter GLUT2.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [24]
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Metadata
- Authors
- Tokarz, V. L., MacDonald, P. E., & Klip, A.
- Affiliations
- University of Toronto (CA)
- University of Alberta (CA)
- Corresponding author
- Klip, Amira
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2018-04-05
- Volume
- 217
- Issue
- 7
- Pages
- 2273-2289
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC6028526
- OpenAlex
- W2796003794
- Cited by
- 471
- References
- 223
- Citations by year
- 2026: 37 · 2025: 63 · 2024: 46 · 2023: 64 · 2022: 80 · 2021: 88 · 2020: 41 · 2019: 41 · 2018: 10
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (FRN 148451, FRN: FND-143203)
- University of Toronto
- The Hospital for Sick Children
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- insulin, insulin biosynthesis, pancreatic beta cells, insulin secretion, hepatic insulin clearance, muscle glucose uptake, adipocyte glucose uptake, insulin signaling, vesicle trafficking, diabetes mellitus
- MeSH terms
- Adipose Tissue, Diabetes Mellitus, Glucose, Humans, Insulin, Insulin Resistance, Adipocytes, Muscle, Skeletal, Testosterone Congeners, Insulin-Secreting Cells
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