ArticleJCI insight2018
Androgen excess in pancreatic β cells and neurons predisposes female mice to type 2 diabetes.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies.Molecular metabolism · 2020Pooled it
- Effects of sex hormones on the development of diabetes and pancreatic islet gene expression in obese type 2 diabetes model ZFDM rat.Experimental animals · 2026Article
- Sex steroids, SHBG and type 2 diabetes in women: what do we really know?Diabetologia · 2026Review
- Advances and challenges in the mechanistic understanding of beta-cell dysfunction in gestational diabetes mellitus.Journal of animal science · 2026Review
- Potential role of maintaining physiological testosterone levels in improving glucose metabolism among normal-weight Japanese women: a pilot exploratory study.Frontiers in endocrinology · 2026Article
- Liver androgen receptor knockout attenuates high-fructose diet-induced glucose dysregulation in female mice.American journal of physiology. Endocrinology and metabolism · 2025Article
- Hepatic Mechanisms of Myocardial Infarction: A New Perspective in Metabolic Dysfunction-Associated Fatty Liver Disease.Journal of the American Heart Association · 2025Review
- AR PROTACs for PCOS: A Long-awaited Breakthrough?Endocrinology · 2025Article
- High-Fat Diet and Metabolic Diseases: A Comparative Analysis of Sex-Dependent Responses and Mechanisms.International journal of molecular sciences · 2025Review
- The Molecular Basis of Polycystic Ovary Syndrome and Its Cardiometabolic Correlates: Exploring the Intersection and Its Clinical Implications-A Narrative Review.Biomedicines · 2025Review
- Review
- Sulfation pathways in the maintenance of functional beta-cell mass and implications for diabetes.Essays in biochemistry · 2024Review
- Upregulation of inflammatory genes and pathways links obesity to severe COVID-19.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.Research square · 2024Article
- Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.bioRxiv : the preprint server for biology · 2024Article
- Sex differences in energy metabolism: natural selection, mechanisms and consequences.Nature reviews. Nephrology · 2024Review
- Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents.Nutrients · 2023Review
- Central androgen action reverses hypothalamic astrogliosis and atherogenic risk factors induced by orchiectomy and high-fat diet feeding in male mice.American journal of physiology. Endocrinology and metabolism · 2023Article
- Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment.Journal of ovarian research · 2023Review
- Advances in mitochondria-centered mechanism behind the roles of androgens and androgen receptor in the regulation of glucose and lipid metabolism.Frontiers in endocrinology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Androgen excess predisposes women to type 2 diabetes (T2D), but the mechanism of this is poorly understood. We report that female mice fed a Western diet and exposed to chronic androgen excess using dihydrotestosterone (DHT) exhibit hyperinsulinemia and insulin resistance associated with secondary pancreatic β cell failure, leading to hyperglycemia. These abnormalities are not observed in mice lacking the androgen receptor (AR) in β cells and partially in neurons of the mediobasal hypothalamus (MBH) as well as in mice lacking AR selectively in neurons. Accordingly, i.c.v. infusion of DHT produces hyperinsulinemia and insulin resistance in female WT mice. We observe that acute DHT produces insulin hypersecretion in response to glucose in cultured female mouse and human pancreatic islets in an AR-dependent manner via a cAMP- and mTOR-dependent pathway. Acute DHT exposure increases mitochondrial respiration and oxygen consumption in female cultured islets. As a result, chronic DHT exposure in vivo promotes islet oxidative damage and susceptibility to additional stress induced by streptozotocin via AR in β cells. This study suggests that excess androgen predisposes female mice to T2D following AR activation in neurons, producing peripheral insulin resistance, and in pancreatic β cells, promoting insulin hypersecretion, oxidative injury, and secondary β cell failure.
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.