Disproportionate elevation of immunoreactive proinsulin in Type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance
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In this study, we found that the ratio of proinsulin to total immunoreactive insulin was much higher in 22 patients with Type 2 (non-insulin-dependent) diabetes mellitus than in 28 non-diabetic control subjects of similar age and adiposity (32 +/- 3 vs 15 +/- 1%, p less than 0.001). In addition, the arginine-induced acute proinsulin response to total immunoreactive insulin response ratio was greater in diabetic patients (n = 10) than in control subjects (n = 9) (8 +/- 2 vs 2 +/- 0.5%, p = 0.009), suggesting that increased islet secretion per se accounted for the increased ratio of proinsulin to immunoreactive insulin. One explanation for these findings is that increased demand for insulin in the presence of islet dysfunction leads to a greater proportion of proinsulin secreted from the B cell. We tested this hypothesis by comparing proinsulin secretion before and during dexamethasone-induced insulin resistance in diabetic patients and control subjects. Dexamethasone treatment (6 mg/day for 3 days) raised the proinsulin to immunoreactive insulin ratio in control subjects from 13 +/- 2 to 21 +/- 2% (p less than 0.0001) and in diabetic patients from 29 +/- 5 to 52 +/- 7% (p less than 0.001). Dexamethasone also raised the ratio of the acute proinsulin response to the acute immunoreactive insulin response in control subjects from 2 +/- 0.5 to 5 +/- 2% (p = 0.01) and in diabetic patients from 8 +/- 2 to 14 +/- 4% (p = NS), suggesting that the dexamethasone-induced increment in the basal ratio of proinsulin to immunoreactive insulin was also due to increased secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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In established Type 2 diabetes, there is inefficient proinsulin processing to insulin and a reduction in the release of islet amyloid polypeptide (IAPP)/amylin.
“inefficient proinsulin processing to insulin [77, 78, 79, 80, 81, 82, 83] and a reduction in the release of islet amyloid polypeptide (IAPP), known also as amylin [84, 85, 86, 87], have been observed in established Type 2 diabetes.”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [78]
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- Authors
- Ward, W. K., LaCava, E. C., Paquette, T. L., Beard, J. C., Wallum, B. J., & Porte, D.
- Affiliations
- University of Washington (US)
- Venue
- Diabetologia
- Published
- 1987-09
- Volume
- 30
- Issue
- 9
- Pages
- 698-702
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2043209055
- Cited by
- 275
- References
- 13
- Citations by year
- 2025: 2 · 2023: 8 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 2 · 2012: 3
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p30am017047-11, RR-37, 5r01am012829-17)
- National Center for Research Resources (RR 37)
- Topics
- Health Sciences › Medicine › Surgery › 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
- proinsulin, type 2 diabetes, insulin resistance, beta-cell secretion, dexamethasone, islet dysfunction, insulin requirement, obesity
- MeSH terms
- Arginine, Blood Glucose, Dexamethasone, Diabetes Mellitus, Diabetes Mellitus, Type 2, Female, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Proinsulin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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