# Hepatic Rap1 in glucose homeostasis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $452,460

## Abstract

Type 2 diabetes (T2D) and its complications constitute a significant public health problem worldwide. Individuals with T2D are more prone to developing metabolic and cardiovascular diseases. Majority of T2D patients are treated with the cholesterol-lowering drugs, statins, to decrease the risk of developing heart disease. Paradoxically, statins have recently been linked to development of new-onset T2D; however, the underlying mechanisms are not known. This proposal is based on an exciting new finding from our laboratory suggesting that the small G protein of the Ras superfamily, Rap1a, plays a major role in glucose homeostasis. We propose that hepatic Rap1a is a novel regulator of hepatic glucose production (HGP) and inhibition of its activity contributes to statin-induced glucose intolerance and hyperglycemia. Based on these, we will determine the in vivo role of hepatic Rap1a in glucose homeostasis (Aim 1), elucidate it’s in role statin- mediated glucose intolerance and hyperglycemia (Aim 2), and explore molecular hypotheses explaining how Rap1a regulates HGP (Aim 3). We will test these new ideas in vivo and ex vivo, using a combination of mouse genetic, physiological and biochemical approaches. The proposed studies will uncover a novel mechanism of glucose homeostasis, which can be exploited for future therapeutic strategies to reduce T2D incidence.

## Key facts

- **NIH application ID:** 10140337
- **Project number:** 5R01DK124457-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Lale Ozcan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $452,460
- **Award type:** 5
- **Project period:** 2020-04-07 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140337

## Citation

> US National Institutes of Health, RePORTER application 10140337, Hepatic Rap1 in glucose homeostasis (5R01DK124457-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10140337. Licensed CC0.

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