ArticleCancer & metabolism2022
Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics.
Article in Cancer & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Research trends and knowledge structure of pancreatic cancer and type 2 diabetes mellitus research: a two-decade CiteSpace analysis.Frontiers in endocrinology · 2026Pooled it
- An Insulin-Exosome-TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development.Nature communications · 2026Article
- Is Insulin Resistance the Driver or the Outcome of Diabetes Mellitus? A Critical Review.Journal of nutrition and metabolism · 2026Review
- Pancreatic Cancer and Diabetes: Insights, Hypotheses, and Next Steps.International journal of molecular sciences · 2025Review
- The complex interplay between diabetes mellitus and pancreatic carcinogenesis: deciphering multifactorial mechanisms and identifying emerging therapeutic vulnerabilities.Cell & bioscience · 2025Review
- Unusual Manifestations of Primary Pancreatic Neoplasia.Cancers · 2025Review
- Triglyceride-glucose index and cancer risk: a prospective cohort study in Taiwan.Diabetology & metabolic syndrome · 2025Article
- An Analysis of the mRNA Expression of Peripheral-Blood Stem and Progenitor Cell Markers in Pancreatic Neoplastic Disorders.Current issues in molecular biology · 2025Article
- Diabetes and its Silent Partner: A Critical Review of Hyperinsulinemia and its Complications.Current diabetes reviews · 2025Review
- Correlation Between Antihypertensive Drugs and Survival Among Patients with Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Association Between Physical Activity and Pancreatic Cancer Risk and Mortality: A Systematic Review and Meta-Analysis.Cancers · 2024Review
- Diabetic ketoacidosis as first presentation of undiagnosed pancreatic cancer in an octogenarian.Endocrinology, diabetes & metabolism case reports · 2024Article
- Prognostic significance of glucose-lipid metabolic index in pancreatic cancer patients with diabetes mellitus.Cancer medicine · 2024Article
- Review
- Exploring the Role of Hyperinsulinemia in Obesity-Associated Tumor Development.Cancer research · 2024Article
- Decoding the obesity-cancer connection: lessons from preclinical models of pancreatic adenocarcinoma.Life science alliance · 2023Review
- Leptin: A Heavyweight Player in Obesity-Related Cancers.Biomolecules · 2023Review
- Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings.Diabetes · 2023Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundHyperinsulinemia is independently associated with increased risk and mortality of pancreatic cancer. We recently reported that genetically reduced insulin production resulted in ~ 50% suppression of pancreatic intraepithelial neoplasia (PanIN) precancerous lesions in mice. However, only female mice remained normoglycemic, and only the gene dosage of the rodent-specific Ins1 alleles was tested in our previous model. Moreover, we did not delve into the molecular and cellular mechanisms associated with modulating hyperinsulinemia.
methodsWe studied how reduced Ins2 gene dosage affects PanIN lesion development in both male and female Ptf1a
resultsHigh-fat diet-induced hyperinsulinemia was transiently or modestly reduced in female and male mice, respectively, with only one allele of Ins2. This occurred without dramatically affecting glucose tolerance. Genetic reduction of insulin production resulted in mice with a tendency for less PanIN and acinar-to-ductal metaplasia (ADM) lesions. Using single-cell transcriptomics, we found hyperinsulinemia affected multiple cell types in the pancreas, with the most statistically significant effects on local immune cell types that were highly represented in our sampled cell population. Specifically, hyperinsulinemia modulated pathways associated with protein translation, MAPK-ERK signaling, and PI3K-AKT signaling, which were changed in epithelial cells and subsets of immune cells.
conclusionsThese data suggest a potential role for the immune microenvironment in hyperinsulinemia-driven PanIN development. Together with our previous work, we propose that mild suppression of insulin levels may be useful in preventing pancreatic cancer by acting on multiple cell types.
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