Evidence of Cosecretion of Islet Amyloid Polypeptide and Insulin by β-Cells
Open accessAbstract
Islet amyloid polypeptide (IAPP) has been identified as the major constituent of the pancreatic amyloid of non-insulin-dependent diabetes mellitus (NIDDM) and is also present in normal β-cell secretory granules. To determine whether IAPP is a pancreatic secretory product, we measured the quantity of lAPP-like immunoreactivity (IAPP-LI), insulin, and glucagon released into 5 ml of incubation medium during a 2-h incubation of monolayer cultures (n = 5) of neonatal (3- to 5-day-old) Sprague-Dawley rat pancreases under three conditions: 1.67 mM glucose, 16.7 mM glucose, and 16.7 mM glucose plus 10 mM arginine and 0.1 mM isobutylmethylxanthine (IBMX). The quantity of IAPP-LI, insulin, and glucagon in the cell extract was also determined. Mean ± SE IAPP-LI in the incubation medium increased from 0.041 ± 0.003 pmol in 1.67 mM glucose to 0.168 ± 0.029 pmol in 16.7 mM glucose (P < 0.05) and 1.02 ± 0.06 pmol in 16.7 mM glucose plus arginine and IBMX (P < 0.05 vs. 1.67 or 16.7 mM glucose). Insulin secretion increased similarly from 4.34 ± 0.27 to 20.2 ± 0.6 pmol (P < 0.05) and then to 135 ± 5 pmol (P < 0.05 vs. 1.67 or 16.7 mM glucose). Glucagon release tended to decrease with the increase in glucose concentration (0.39 ± 0.01 vs. 0.33 ± 0.02 pmol, P < 0.1), whereas with the addition of arginine and IBMX to high glucose, glucagon release increased to 1.32 ± 0.03 pmol (P < 0.05 vs. 1.67 or 16.7 mM glucose). Thus, the molar proportion of IAPP-LI to insulin secreted in low glucose was ∼1% and did not differ significantly with stimulation (0.95 ± 0.08 vs. 0.84 ± 0.15 vs. 0.76 ± 0.05%). In contrast, there was no constant proportional relationship between the release of IAPP-LI and glucagon (10.6 ± 0.8 vs. 51.3 ± 8.7 vs. 77.5 ± 5.2%). After incubation in 1.67 mM glucose, the extracted cells contained 3.7 ± 0.2 pmol IAPP-LI, 944 ± 25 pmol insulin, and 28.2 ±1.5 pmol glucagon. After maximal stimulation, the fractional release of IAPP-LI was 26.7 ± 0.7% vs. 14.7 ± 0.6% of insulin and 4.4 ± 0.2% of glucagon. These data indicate that nondiabetic neonatal rat islet cultures contain IAPP-LI and release it after stimulation by glucose and nonglucose secretagogues. Furthermore, the data suggest that IAPP-LI is a product of the β-cell, which coreleases it with insulin in a molar ratio of ∼1.100.
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IAPP is co-localized within the same secretory granules as insulin and is typically co-released with insulin in vitro in response to glucose and non-glucose secretagogues.
“IAPP is co-localized within the same secretory granules as insulin [115] and is typically co-released with insulin in vitro in response to glucose and non-glucose secretagogues [116, 117].”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [116]
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- Authors
- Kahn, S. E., D'Alessio, D. A., Schwartz, M. W., Fujimoto, W. Y., Ensinck, J. W., Taborsky, G. J., & Porte, D.
- Affiliations
- University of Washington (US)
- Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington and Veterans Affairs Medical Center Seattle, Washington
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1990-05-01
- Volume
- 39
- Issue
- 5
- Pages
- 634-638
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2159489160
- Cited by
- 454
- References
- 25
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 16 · 2023: 14 · 2022: 13 · 2021: 15 · 2020: 15 · 2019: 16 · 2018: 16 · 2017: 18 · 2016: 20 · 2015: 23 · 2014: 15 · 2013: 16 · 2012: 17
- FWCI
- 28.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 02456, DK07247, DK-03497, T32DK007247)
- 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
- amylin, insulin, pancreatic beta cells, insulin secretion, glucagon secretion, arginine stimulation, 3-isobutyl-1-methylxanthine, glucose stimulation, pancreatic islets, type 2 diabetes, secretory granules, islet transplantation
- MeSH terms
- Amyloid, Animals, Cells, Cultured, Glucose, Insulin, Islets of Langerhans, Rats, Inbred Strains, Rats, Islet Amyloid Polypeptide
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