Cellular Profile of Subfornical Organ Insulin Receptors in Mice.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Neurons*/metabolism ; Receptor, Insulin*/metabolism ; Receptor, Insulin*/genetics ; Subfornical Organ*/metabolism; Animals ; Male ; Mice ; Astrocytes/metabolism ; Insulin/metabolism ; Mice, Inbred C57BL ; Receptor, Angiotensin, Type 1/metabolism ; Receptor, Angiotensin, Type 1/genetics ; Signal Transduction

Brain insulin receptor signaling is strongly implicated in cardiovascular and metabolic physiological regulation. In particular, we recently demonstrated that insulin receptors within the subfornical organ (SFO) play a tonic role in cardiovascular and metabolic regulation in mice. The SFO is a forebrain sensory circumventricular organ that regulates cardiometabolic homeostasis due to its direct exposure to the circulation and thus its ability to sense circulating factors, such as insulin. Previous work has demonstrated broad distribution of insulin receptor-expressing cells throughout the entire SFO, indirectly indicating insulin receptor expression in multiple cell types. Based on this, we sought to determine the cellular phenotypes that express insulin receptors within the SFO by combining immunohistochemistry with genetically modified reporter mouse models. Interestingly, SFO neurons, including both excitatory and inhibitory types, were the dominant cell site for insulin receptor expression, although a weak degree of insulin receptor expression was also detected in astrocytes. Moreover, SFO angiotensin type 1a receptor neurons also expressed insulin receptors. Collectively, these anatomical findings indicate the existence of potentially complex cellular networks within the SFO through which insulin signaling can influence physiology and further point to the SFO as a possible brain site for crosstalk between angiotensin-II and insulin.

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R01DK117007 National Institute of Health, NIDDK; R01HL141393 National Institue of Health, NHLBI; 19CDA34630010 American Heart Association; AHA932522 American Heart Association

Keywords: angiotensin-II; astrocytes; circumventricular organ; insulin; neurons

0 (Insulin)
0 (Receptor, Angiotensin, Type 1)
EC 2.7.10.1 (Receptor, Insulin)
0 (Insr protein, mouse)

Date Created: 20241026 Date Completed: 20241026 Latest Revision: 20250319

20250319

PMC11506324

10.3390/biom14101256

39456189