Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility
Open accessAbstract
Circulating leptin and insulin convey information regarding energy stores to the central nervous system, particularly the hypothalamus. Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis and express leptin and insulin receptors. However, the physiological significance of concomitant leptin and insulin action on POMC neurons remains to be established. Here, we show that mice lacking both leptin and insulin receptors in POMC neurons (Pomc-Cre, Lepr(flox/flox) IR(flox/flox) mice) display systemic insulin resistance, which is distinct from the single deletion of either receptor. In addition, Pomc-Cre, Lepr(flox/flox) IR(flox/flox) female mice display elevated serum testosterone levels and ovarian abnormalities, resulting in reduced fertility. We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function.
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Female mice lacking both insulin and leptin receptors in POMC neurons exhibit marked hepatic insulin resistance.
“female mice lacking both insulin- and leptin-receptors in POMC neurons exhibited marked hepatic insulin resistance, as measured using the euglycemic-hyperinsulinemic clamp technique (83)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [83]
Actions of both insulin and leptin on discrete subpopulations of POMC neurons act synergistically to suppress hepatic glucose production.
“suggesting that actions of both insulin and leptin on discrete subpopulations of POMC neurons act synergistically to suppress HGP.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [83]
The effects of insulin and leptin on hypothalamic POMC cells are mediated on distinct proopiomelanocortin neuronal subsets.
“these effects are in fact mediated on distinct proopiomelanocortin neuronal subsets (37,38).”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [37]
Both insulin and leptin exert PI3K-dependent effects on hypothalamic POMC cells.
“although both hormones exert phosphatidylinositol-3-OH kinase-dependent effects on hypothalamic POMC cells”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [37]
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References 85 · Cited by 391
Research works printed but not linked: 1
- Williams KW Margatho LO Lee CE Choi M Lee S Scott MM Elias CF Elmquist JK 2010 Marked segregation of acute leptin and insulin effects in distinct populations of arcuate POMC neurons Neuron In press PMC2836776 20164331
- Authors
- Hill, J. W., Elias, C. F., Fukuda, M., Williams, K. W., Berglund, E. D., Holland, W. L., Cho, Y.-R., Chuang, J.-C., Xu, Y., Choi, M., Lauzon, D., Lee, C. E., Coppari, R., Richardson, J. A., Zigman, J. M., Chua, S., Scherer, P. E., Lowell, B. B., Brüning, J. C., & Elmquist, J. K.
- Affiliations
- University of Toledo (US)
- The University of Texas Southwestern Medical Center (US)
- Albert Einstein College of Medicine (US)
- Beth Israel Deaconess Medical Center (US)
- University of Cologne (DE)
- Corresponding author
- Elmquist, Joel K.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 11
- Issue
- 4
- Pages
- 286-297
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2854520
- OpenAlex
- W2110005146
- Cited by
- 391
- References
- 85
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 13 · 2023: 19 · 2022: 22 · 2021: 25 · 2020: 15 · 2019: 16 · 2018: 21 · 2017: 38 · 2016: 23 · 2015: 24 · 2014: 28 · 2013: 43 · 2012: 42
- FWCI
- 17.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5f32dk066972-04, 1tl1dk081181-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (TL1-DK081181, P01DK56116, PL1DK081182, RL1DK081185, R01DK53301, P01DK056116, R01DK053301, 1F32DK066972, R37DK053301, F32 DK066972, K99DK085330)
- National Center for Research Resources (UL1RR024923)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD056491, R01HD061539, U54HD028934, U54-HD-28934)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin, leptin, proopiomelanocortin neurons, hypothalamus, glucose homeostasis, insulin resistance, fertility, reproductive function, leptin receptor, insulin receptor, energy balance, testosterone, ovarian abnormalities
- MeSH terms
- Insulin Secretion, Analysis of Variance, Animals, Blood Glucose, Female, Fertility, Homeostasis, Hypothalamus, Insulin, Insulin Resistance, Islets of Langerhans, Male, Neurons, Pro-Opiomelanocortin, Testosterone, Leptin, Mice
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