# Role of tubuloglomerular feedback in the development of hypertension in diabetes

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2020 · $591,074

## Abstract

There are more than 29 million Americans suffering from diabetes. About 30-40% of patients with diabetes
will eventually develop diabetic nephropathy, which is the leading cause of end stage renal disease in the United
States. The rate of hypertension is more than twice in diabetic patients than the non-diabetic population. Diabetic
patients with hypertension exhibit increased cardiovascular risk and exacerbation of diabetic nephropathy,
however, the mechanisms for hypertension in diabetic patients remains unclear.
 The present proposal will test the central hypothesis that the increase of glucose concentration at the macula
densa in diabetes activates SGLT1, which enhances NOS1 activity and promotes the development of glomerular
hyperfiltration. Inadequate NO generation by the macula densa induces hypertension in diabetes and
exacerbates diabetic kidney injury by mechanisms of limiting elevations in GFR and impairing sodium excretion.
This hypothesis will be tested with the following specific aims:
 Aim 1. Hypothesis: Glucose at the macula densa activates SGLT1 and enhances expression and activity of
macula densa NOS1 splice variants by phosphorylation of Ser1412. Blunted TGF responsiveness mediated by
the macula densa NOS1 promotes the development of hyperfiltration in type 1 and type 2 diabetes.
 Aim 2. Hypothesis: Inadequate NO generation by the macula densa induces hypertension and exacerbates
diabetic kidney injury in type 1 and type 2 diabetes. The mechanism involved is that enhanced TGF response
limits the development of glomerular hyperfiltration, which impairs renal sodium excretion and pressure
natriuresis in diabetes.

## Key facts

- **NIH application ID:** 9917816
- **Project number:** 5R01HL142814-02
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** RUISHENG LIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $591,074
- **Award type:** 5
- **Project period:** 2019-04-19 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917816

## Citation

> US National Institutes of Health, RePORTER application 9917816, Role of tubuloglomerular feedback in the development of hypertension in diabetes (5R01HL142814-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9917816. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*