ArticleDiabetes2016
PKCζ Is Essential for Pancreatic β-Cell Replication During Insulin Resistance by Regulating mTOR and Cyclin-D2.
Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Using animal models to decipher the role of polyamines in the pancreas and β Cell.Amino acids · 2026Review
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- SNRK modulates mTOR-autophagy pathway for liver lipid homeostasis in MAFLD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system.Science translational medicine · 2024Article
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Therapeutic Strategies Targeting Pancreatic Islet β-Cell Proliferation, Regeneration, and Replacement.Endocrinology · 2022Article
- Nrf2 Regulates β-Cell Mass by Suppressing β-Cell Death and Promoting β-Cell Proliferation.Diabetes · 2022Article
- Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells.Frontiers in endocrinology · 2022Review
- Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans.Scientific reports · 2021Article
- Protein kinase C-θ knockout decreases serum IL-10 levels and inhibits insulin secretion from islet β cells.Islets · 2021Article
- Potential Role of Natural Plant MedicineJournal of diabetes research · 2021Review
- Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway.Diabetologia · 2020Article
- Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.Science signaling · 2019Article
- Myc Is Required for Adaptive β-Cell Replication in Young Mice but Is Not Sufficient in One-Year-Old Mice Fed With a High-Fat Diet.Diabetes · 2019Article
- mTOR is a Key Protein Involved in the Metabolic Effects of Simple Sugars.International journal of molecular sciences · 2019Review
- Lipotoxicity andJournal of the Endocrine Society · 2019Review
- Article
- (Re)generating Human Beta Cells: Status, Pitfalls, and Perspectives.Physiological reviews · 2018Review
- Episodic β-cell death and dedifferentiation during diet-induced obesity and dysglycemia in male mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
Corrections and comments
- Commented on by
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Adaptive β-cell replication occurs in response to increased metabolic demand during insulin resistance. The intracellular mediators of this compensatory response are poorly defined and their identification could provide significant targets for β-cell regeneration therapies. Here we show that glucose and insulin in vitro and insulin resistance in vivo activate protein kinase C ζ (PKCζ) in pancreatic islets and β-cells. PKCζ is required for glucose- and glucokinase activator-induced proliferation of rodent and human β-cells in vitro. Furthermore, either kinase-dead PKCζ expression (KD-PKCζ) or disruption of PKCζ in mouse β-cells blocks compensatory β-cell replication when acute hyperglycemia/hyperinsulinemia is induced. Importantly, KD-PKCζ inhibits insulin resistance-mediated mammalian target of rapamycin (mTOR) activation and cyclin-D2 upregulation independent of Akt activation. In summary, PKCζ activation is key for early compensatory β-cell replication in insulin resistance by regulating the downstream signals mTOR and cyclin-D2. This suggests that alterations in PKCζ expression or activity might contribute to inadequate β-cell mass expansion and β-cell failure leading to type 2 diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.