ArticleBiology of reproduction2018
Elevated androgen levels induce hyperinsulinemia through increase in Ins1 transcription in pancreatic beta cells in female rats.
Article in Biology of reproduction, 2018. 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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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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Genetic associations with polycystic ovary syndrome: the role of the mitochondrial genome; a systematic review and meta-analysis.Journal of clinical pathology · 2022Pooled it
- Sex steroids, SHBG and type 2 diabetes in women: what do we really know?Diabetologia · 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
- Narrative review of metabolic syndrome and its relationships with non-alcoholic fatty liver disease, gonadal dysfunction and obstructive sleep apnea.Diabetology & metabolic syndrome · 2025Review
- Juvenile Granulosa Cell Tumor Mimicking HAIR-AN in a 4-year-old: A Case ReportJournal of clinical research in pediatric endocrinology · 2024Article
- Androgen-induced upregulation of CFTR in pancreatic β-cell contributes to hyperinsulinemia in PCOS model.Endocrine · 2024Article
- Placental Fatty Acid Metabolism and Transport in a Rat Model of Gestational Diabetes Mellitus.Journal of women's health and development · 2023Article
- Effect of crude polysaccharide from seaweed, Dictyopteris divaricata (CDDP) on gut microbiota restoration and anti-diabetic activity in streptozotocin (STZ)-induced T1DM mice.Gut pathogens · 2022Article
- The Antidiabetic Effects and Modes of Action of thePharmaceutics · 2022Article
- [Correlation between total testosterone levels and insulin resistance in patients with acanthosis nigricans and non-acanthosis nigrican].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Hyperandrogenemia in Early Adulthood Is an Independent Risk Factor for Abnormal Glucose Metabolism in Middle Age.The Journal of clinical endocrinology and metabolism · 2021Article
- Effects of dietary active soybean trypsin inhibitors on pancreatic weights, histology and expression of STAT3 and receptors for androgen and estrogen in different tissues of rats.Molecular biology reports · 2021Article
- Androgens impair β-cell function in a mouse model of polycystic ovary syndrome by activating endoplasmic reticulum stress.Endocrine connections · 2021Article
- Musa paradisiaca L. leaf and fruit peel hydroethanolic extracts improved the lipid profile, glycemic index and oxidative stress in nicotinamide/streptozotocin-induced diabetic rats.Veterinary medicine and science · 2021Article
- The role of androgen and its related signals in PCOS.Journal of cellular and molecular medicine · 2021Review
- Mitochondria in Sex Hormone-Induced Disorder of Energy Metabolism in Males and Females.Frontiers in endocrinology · 2021Review
- Molecular Insulin Actions Are Sexually Dimorphic in Lipid Metabolism.Frontiers in endocrinology · 2021Review
- Intertwined reproductive endocrinology: Puberty and polycystic ovary syndrome.Current opinion in endocrine and metabolic research · 2020Article
- Article
- Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin.Archives of endocrinology and metabolism · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in adult females. We tested whether androgens dysregulate pancreatic beta cell function to induce hyperinsulinemia through transcriptional regulation of insulin gene (Ins) in the islets. Adult female Wistar rats implanted with dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia with increased HOMA-IR index in fasting state and glucose intolerance and exaggerated insulin responses following glucose tolerance test. DHT females had no change in islet number, size and beta cell proliferation/apoptosis but exhibited significant mitochondrial dysfunction (higher ADP/ATP ratio, decreased mtDNA copy number, increased reactive oxygen production and downregulation of mitochondrial biogenesis) and enhanced glucose-stimulated insulin secretion. Ins expression was increased in DHT islets. In vitro incubation of control islets with DHT dose dependently stimulated Ins transcription. Analysis of Ins1 gene revealed a putative androgen responsive element in the promoter. Chromatin-immunoprecipitation assays showed that androgen receptors bind to this element in response to DHT stimulation. Furthermore, reporter assays showed that the promoter element is highly responsive to androgens. Insulin-stimulated glucose uptake in skeletal muscle was decreased with associated decrease in IRβ expression in DHT females. Our studies identified a novel androgen-mediated mechanism for the control of Ins expression via transcriptional regulation providing a molecular mechanism linking elevated androgens and hyperinsulemia. Decreased IRβ expression in the skeletal muscles may contribute, in part, to glucose intolerance in this model.
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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.