ArticleThe Journal of clinical investigation1995
Increased secretory demand rather than a defect in the proinsulin conversion mechanism causes hyperproinsulinemia in a glucose-infusion rat model of non-insulin-dependent diabetes mellitus.
Article in The Journal of clinical investigation, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 92 citations in OpenAlex.
- Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis.Diabetes · 2022Trial
- The effect of different volumes of high-intensity interval training on proinsulin in participants with the metabolic syndrome: a randomised trial.Diabetologia · 2016Trial
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Molecular and cellular biology · 2019Article
- Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.Annals of the New York Academy of Sciences · 2018Review
- β-Cell Failure or β-Cell Abuse?Frontiers in endocrinology · 2018Review
- INS-gene mutations: from genetics and beta cell biology to clinical disease.Molecular aspects of medicine · 2015Review
- Article
- Inefficient translocation of preproinsulin contributes to pancreatic β cell failure and late-onset diabetes.The Journal of biological chemistry · 2014Article
- Islet β cell mass in diabetes and how it relates to function, birth, and death.Annals of the New York Academy of Sciences · 2013Review
- Islet neogenesis: a possible pathway for beta-cell replenishment.The review of diabetic studies : RDS · 2012Review
- Dual and opposing roles of the unfolded protein response regulated by IRE1alpha and XBP1 in proinsulin processing and insulin secretion.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- β-Cell dysfunction under hyperglycemic stress: a molecular model.Journal of diabetes science and technology · 2010Article
- Extranuclear estrogen receptor-alpha stimulates NeuroD1 binding to the insulin promoter and favors insulin synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Endoplasmic reticulum overcrowding as a mechanism of beta-cell dysfunction in diabetes.Biophysical journal · 2010Article
- Effect of glucagon-like peptide-1 on beta- and alpha-cell function in isolated islet and whole pancreas transplant recipients.The Journal of clinical endocrinology and metabolism · 2009Article
- Treatment with an Interleukin 1 beta antibody improves glycemic control in diet-induced obesity.Cytokine · 2008Article
- The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6.Endocrinology · 2008Article
- Association of fasting glucagon and proinsulin concentrations with insulin resistance.Diabetologia · 2007Article
- Regulation of pancreatic PC1 and PC2 associated with increased glucagon-like peptide 1 in diabetic rats.The Journal of clinical investigation · 2000Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperproinsulinemia in non-insulin-dependent diabetes mellitus (NIDDM) is due to an increased release of proinsulin from pancreatic beta cells. This could reside in increased secretory demand placed on the beta cell by hyperglycemia or in the proinsulin conversion mechanism. In this study, biosynthesis of the proinsulin conversion enzymes (PC2, PC3, and carboxypeptidase-H [CP-H]) and proinsulin, were examined in islets isolated from 48-h infused rats with 50% (wt/vol) glucose (hyperglycemic, hyperinsulinemic, and increased pancreatic proinsulin to insulin ratio), 20% (wt/vol) glucose (normoglycemic but hyperinsulinemic), and 0.45% (wt/vol) saline (controls). A decrease in the islet content of PC2, PC3, and CP-H from hyperglycemic rats was observed. This reduction did not correlate with any deficiency in mRNA levels or biosynthesis of PC2, PC3, CP-H, or proinsulin. Furthermore, proinsulin conversion rate was comparable in islets from hyperglycemic and control rats. However, in islets from hyperglycemic rats an abnormal increased proportion of proinsulin was secreted, that was accompanied by an augmented release of PC2, PC3 and CP-H. Stimulation of the beta cell's secretory pathway by hyperglycemia, resulted in proinsulin being prematurely secreted from islets before its conversion could be completed. Thus, hyperproinsulinemia induced by chronic hyperglycemia likely results from increased beta cell secretory demand, rather than a defect in the proinsulin processing enzymes per se.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.