Selective insulin action on skin, ovary, and heart in insulin-resistant states
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States of hyperinsulinemia with resistance to insulin action on glucose disposal are frequently associated with proliferative tissue abnormalities of the skin (acanthosis nigricans), ovary, and heart. That insulin may be involved in the pathogenesis of these growth-related abnormalities despite resistance to its metabolic effects mediated through the insulin receptor is suggested by the known ability of high concentrations of insulin to stimulate DNA synthesis and cell proliferation in vitro through the insulin-like growth factor I (IGF-I) receptor. IGF-I receptors are present in skin keratinocytes, some ovarian tissue compartments, and in the heart. Furthermore, ovarian tissue from hyperinsulinemic insulin-resistant women responds to supraphysiologic insulin concentrations in vitro by enhanced steroidogenesis. Cultured, transformed T-lymphocytes from an infant with leprechaunism fail to augment basal-colony formation in response to physiologic insulin concentrations in vitro (compared to a doubling seen in normal subjects), but respond normally to supraphysiologic insulin concentrations, the effect of which is competitively inhibited by a monoclonal antibody to the IGF-I receptor. Thus, insulin action mediated through the IGF-I receptor may initiate growth-promoting tissue effects in the face of limited insulin effect on glucose metabolism. Such spillover actions may add to the morbidity associated with states of clinical insulin resistance.
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In PCOS, liver, skeletal muscle, and adipose tissue exhibit insulin resistance, whereas steroid-producing tissues and the pituitary retain insulin sensitivity.
“This leads to the paradox of insulin signaling in PCOS; liver, skeletal muscle, and adipose tissue exhibit IR, whereas steroid-producing tissues and the pituitary retain insulin sensitivity [71, 72].”
From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [71]
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“All these factors lead to increased testosterone levels.[14,15] In present study, though mean testosterone and LH level improved in each group over the period of 6 months as compared to baseline, but the difference was statistically insignificant (p>0.”
BackgroundPrevalence and Phenotypic Diversity of PCOS in Indian Women: An Observational Study
Khanorkar, N., Kulkarni, P., & Warjukar, E. (2023) · International Journal of Science and Research (IJSR) · doi:10.21275/sr231005091135
“Acanthosisnigricans, when not related to malignancy, is considered to be a dermal manifestation of hyperinsulinaemia (22, 23, 24).”
BackgroundElbahbity, A. R., AbouZeid, A. A., Mohamed, M., et al. (2025) · Egyptian Pediatric Association Gazette · doi:10.1186/s43054-025-00368-5
“…concentration of insulin in DS triggers anabolic effects via insulin-like growth factor-1 (IGF-1) receptors which are expressed in ovarian tissues [5], leading to an abnormal enlargement of the ovaries along with ovarian cysts and possibly ovarian tumors, in addition to biochemical abnormalities…”
Antoniou-Tsigkos, A., Καρράς, Γ., Papagianni, M., CHRISTOPOULOS, P. F., Vlahos, N. F., & Mastorakos, G. M. (2025) · Endocrine · doi:10.1007/s12020-025-04527-x
“Thus, although the above reported tissues demonstrate insulin resistance in PCOS patients, steroidogenesis by steroid-producing organs remains intact to insulin activity [26].”
Ocular Manifestations of Donohue's Syndrome
Gable, E. M., & Brandonisio, T. M. (2003) · Optometry and Vision Science · doi:10.1002/j.1538-9235.2003.tb01650.x
- Authors
- Geffner, M. E., & Golde, D. W.
- Affiliations
- University of California, Los Angeles (US)
- ORCID
- Geffner, Mitchell E
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1988-06-01
- Volume
- 11
- Issue
- 6
- Pages
- 500-505
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2027130419
- Cited by
- 97
- References
- 0
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 1 · 2012: 3
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service
- National Cancer Institute (CA32737, CA30388)
- National Center for Research Resources (RR-865)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Dermatology › Skin Diseases and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin resistance, hyperinsulinemia, IGF-1 receptor, acanthosis nigricans, ovarian steroidogenesis, cardiac growth, keratinocytes, T cell proliferation, leprechaunism, insulin receptor, cell proliferation, DNA synthesis
- MeSH terms
- Acanthosis Nigricans, Female, Cardiomegaly, Humans, Insulin, Insulin Resistance, Cardiomyopathies, Myocardium, Ovarian Diseases, Ovary, Skin
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