Journal article
A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria
eLife, Vol.12, RP92075
07/31/2024
DOI: 10.7554/eLife.91540.4
Abstract
The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body. How the body senses this glucose loss and consequently enhances glucose production is unclear. Using renal Slc2a2 (also known as Glut2 ) knockout mice, we demonstrate that elevated glycosuria activates the hypothalamic-pituitary-adrenal axis, which in turn drives endogenous glucose production. This phenotype was attenuated by selective afferent renal denervation, indicating the involvement of the afferent nerves in promoting the compensatory increase in glucose production. In addition, through plasma proteomics analyses we observed that acute phase proteins - which are usually involved in the body’s defense mechanisms against a threat – were the top candidates which were either upregulated or downregulated in renal Slc2a2 KO mice. Overall, afferent renal nerves contribute to promoting endogenous glucose production in response to elevated glycosuria and loss of glucose in urine is sensed as a biological threat in mice. These findings may be useful in improving the efficiency of drugs like SGLT2 inhibitors that are intended to treat hyperglycemia by enhancing glycosuria but are met with a compensatory increase in endogenous glucose production.
Details
- Title: Subtitle
- A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria
- Creators
- Tumininu S Faniyan - University of Rochester Medical CenterXinyi Zhang - Yale UniversityDonald A Morgan - University of IowaJorge Robles - University of Rochester Medical CenterSiresha Bathina - University of Rochester Medical CenterPaul S Brookes - University of Rochester Medical CenterKamal Rahmouni - University of IowaRachel J Perry - Yale UniversityKavaljit H Chhabra - University of Rochester Medical Center
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.12, RP92075
- DOI
- 10.7554/eLife.91540.4
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Language
- English
- Date published
- 07/31/2024
- Academic Unit
- Neuroscience and Pharmacology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984696659802771
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