Journal article
Renal tubule insulin receptor modestly promotes elevated blood pressure and markedly stimulates glucose reabsorption
JCI insight, Vol.3(16), e95107
08/23/2018
DOI: 10.1172/jci.insight.95107
PMCID: PMC6141164
PMID: 30135311
Abstract
Although the cause of hypertension among individuals with obesity and insulin resistance is unknown, increased plasma insulin, acting in the kidney to increase sodium reabsorption, has been proposed as a potential mechanism. Insulin may also stimulate glucose uptake, but the contributions of tubular insulin signaling to sodium or glucose transport in the setting of insulin resistance is unknown. To directly study the role of insulin signaling in the kidney, we generated inducible renal tubule-specific insulin receptor-KO mice and used high-fat feeding and mineralocorticoids to model obesity and insulin resistance. Insulin receptor deletion did not alter blood pressure or sodium excretion in mice on a high-fat diet alone, but it mildly attenuated the increase in blood pressure with mineralocorticoid supplementation. Under these conditions, KO mice developed profound glucosuria. Insulin receptor deletion significantly reduced SGLT2 expression and increased urinary glucose excretion and urine flow. These data demonstrate a direct role for insulin receptor-stimulated sodium and glucose transport and a functional interaction of insulin signaling with mineralocorticoids in vivo. These studies uncover a potential mechanistic link between preserved insulin sensitivity and renal glucose handling in obesity and insulin resistance.
Details
- Title: Subtitle
- Renal tubule insulin receptor modestly promotes elevated blood pressure and markedly stimulates glucose reabsorption
- Creators
- Jonathan M. Nizar - Stanford UniversityBlythe D. Shepard - Georgetown UniversityVianna T. Vo - Stanford UniversityVivek Bhalla - Stanford University
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.3(16), e95107
- Publisher
- Amer Soc Clinical Investigation Inc
- DOI
- 10.1172/jci.insight.95107
- PMID
- 30135311
- PMCID
- PMC6141164
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Number of pages
- 12
- Grant note
- K08 DK114567-01; K01 DK106400; 1R01 DK091565 / NIH/NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) UL1TR001085 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) UL1 TR001085 / Stanford CTSA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) Tashia and John Morgridge Endowed Postdoctoral Fellowship Stanford Institutes of Medicine Research Internship K08DK114567 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Child Health Research Institute at Stanford University American Heart Association Postdoctoral Fellowship on behalf of the Grossman Family; American Heart Association
- Language
- English
- Date published
- 08/23/2018
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359850702771
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