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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

The insulin gene in humans and mice: evolution, regulation, and sex-specific mechanisms of diabetes susceptibility

  • Ali Mazloum1,2
  • Nikita Batashkov1,2
  • Veronika Ledyaeva1,2
  • Gava Khulkhachiev2
  • Dmitry Tabakov1,2
  • Olga N. Mityaeva1,2
  • Pavel Yu Volchkov1,2,3,4
4 affiliations
  1. 1Moscow Center for Advanced Studies
  2. 2Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
  3. 3Moscow Clinical Scientific Center named after Anatoly Sergeevich (N. A. A. S.) Loginov
  4. 4Faculty of Fundamental Medicine, Lomonosov Moscow State University
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Abstract

The insulin gene (INS) encodes a peptide hormone critical for glucose homeostasis, and its dysregulation underlies both type 1 and type 2 diabetes mellitus. This review compares the structural organization and functional regulation of the insulin gene in humans and mice, highlighting key species differences including the presence of two non-allelic insulin genes (Ins1 and Ins2) in mice versus a single INS gene in humans. Despite these differences, most preclinical diabetes research has historically been conducted in male mice, potentially concealing sex and species specific mechanisms. Additionally, this review examines the growing evidence for sex-specific differences in diabetes susceptibility. Recent single-cell multi-omics studies reveal that human pancreatic islets exhibit sex-specific chromatin accessibility and gene expression patterns, with autosomal sex differences emerging predominantly in type 2 diabetes. The protective effects of estrogen, mediated through estrogen receptor α signaling, contribute to enhanced insulin sensitivity and beta-cell function in premenopausal females. We argue that routine inclusion of both sexes and species aware interpretation of insulin gene studies are prerequisites for precision diabetology.

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Cite

BibTeXRIS
BibTeX
@article{mazloum2026insulin,
  title = {{The insulin gene in humans and mice: evolution, regulation, and sex-specific mechanisms of diabetes susceptibility}},
  author = {Ali Mazloum and Nikita Batashkov and Veronika Ledyaeva and Gava Khulkhachiev and Dmitry Tabakov and Olga N. Mityaeva and Pavel Yu Volchkov},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1954427},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1954427/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The insulin gene in humans and mice: evolution, regulation, and sex-specific mechanisms of diabetes susceptibility
AU  - Ali Mazloum
AU  - Nikita Batashkov
AU  - Veronika Ledyaeva
AU  - Gava Khulkhachiev
AU  - Dmitry Tabakov
AU  - Olga N. Mityaeva
AU  - Pavel Yu Volchkov
PY  - 2026
DA  - 2026/10/20
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1954427
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1954427/full
AB  - The insulin gene (INS) encodes a peptide hormone critical for glucose homeostasis, and its dysregulation underlies both type 1 and type 2 diabetes mellitus. This review compares the structural organization and functional regulation of the insulin gene in humans and mice, highlighting key species differences including the presence of two non-allelic insulin genes (Ins1 and Ins2) in mice versus a single INS gene in humans. Despite these differences, most preclinical diabetes research has historically been conducted in male mice, potentially concealing sex and species specific mechanisms. Additionally, this review examines the growing evidence for sex-specific differences in diabetes susceptibility. Recent single-cell multi-omics studies reveal that human pancreatic islets exhibit sex-specific chromatin accessibility and gene expression patterns, with autosomal sex differences emerging predominantly in type 2 diabetes. The protective effects of estrogen, mediated through estrogen receptor α signaling, contribute to enhanced insulin sensitivity and beta-cell function in premenopausal females. We argue that routine inclusion of both sexes and species aware interpretation of insulin gene studies are prerequisites for precision diabetology.
SN  - 1664-2392
ER  -