ArticlePloS one2011
Altered insulin receptor signalling and β-cell cycle dynamics in type 2 diabetes mellitus.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
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- Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway.Frontiers in pharmacology · 2022Review
- Development of Type 1 Diabetes may occur through a Type 2 Diabetes mechanism.Frontiers in endocrinology · 2022Article
- The Roles of the IGF Axis in the Regulation of the Metabolism: Interaction and Difference between Insulin Receptor Signaling and IGF-I Receptor Signaling.International journal of molecular sciences · 2021Review
- Islet Regeneration: Endogenous and Exogenous Approaches.International journal of molecular sciences · 2021Review
- Expression of Circulating MicroRNAs and Myokines and Interactions with Serum Osteopontin in Type 2 Diabetic Patients with Moderate and Poor Glycemic Control: A Biochemical and Molecular Study.BioMed research international · 2021Article
- The Insulin Receptor Adaptor IRS2 is an APC/C Substrate That Promotes Cell Cycle Protein Expression and a Robust Spindle Assembly Checkpoint.Molecular & cellular proteomics : MCP · 2020Article
- Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2020Review
- Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway.Diabetologia · 2020Article
- Long Non-Coding RNAs as Key Modulators of Pancreatic β-Cell Mass and Function.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
15 authors at 10 institutions in 3 countries.
Funding
Abstract
Insulin resistance, reduced β-cell mass, and hyperglucagonemia are consistent features in type 2 diabetes mellitus (T2DM). We used pancreas and islets from humans with T2DM to examine the regulation of insulin signaling and cell-cycle control of islet cells. We observed reduced β-cell mass and increased α-cell mass in the Type 2 diabetic pancreas. Confocal microscopy, real-time PCR and western blotting analyses revealed increased expression of PCNA and down-regulation of p27-Kip1 and altered expression of insulin receptors, insulin receptor substrate-2 and phosphorylated BAD. To investigate the mechanisms underlying these findings, we examined a mouse model of insulin resistance in β-cells--which also exhibits reduced β-cell mass, the β-cell-specific insulin receptor knockout (βIRKO). Freshly isolated islets and β-cell lines derived from βIRKO mice exhibited poor cell-cycle progression, nuclear restriction of FoxO1 and reduced expression of cell-cycle proteins favoring growth arrest. Re-expression of insulin receptors in βIRKO β-cells reversed the defects and promoted cell cycle progression and proliferation implying a role for insulin-signaling in β-cell growth. These data provide evidence that human β- and α-cells can enter the cell-cycle, but proliferation of β-cells in T2DM fails due to G1-to-S phase arrest secondary to defective insulin signaling. Activation of insulin signaling, FoxO1 and proteins in β-cell-cycle progression are attractive therapeutic targets to enhance β-cell regeneration in the treatment of T2DM.
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Registered trials
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.