# Mechanisms of Cadmium Induced Dysglycemia and Type 2 Diabetes Mellitus

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $391,910

## Abstract

Project summary:
Failure of insulin producing beta cells in the setting of insulin resistance is the main underlying cause for type 2
diabetes mellitus. Genetic susceptibility, age, lifestyle, and environmental factors contribute to beta cell failure
in type-2 diabetes mellitus. Others and we previously published studies showing that low-level chronic
exposure to the non-essential transition metal cadmium (Cd) in the general population is associated with an
increase in the risk of prediabetes and type 2 diabetes mellitus. In recent preliminary studies, we have shown
that in vivo exposure to Cd caused a rise in blood sugar accompanied by altered insulin secretion in mice. We
also found that insulin-producing pancreatic beta cells accumulate Cd avidly, leading to impaired insulin
secretion and an increase in signs of endoplasmatic reticulum stress. The goal of the proposed studies is to
examine the mechanism by which exposure to various, environmentally relevant concentrations of cadmium
impair insulin production from beta cells. Specifically, we will build on our current preliminary data and explore
the hypothesis that accumulation of Cd in insulin producing beta cells causes beta cell toxicity by impairing
normal zinc medicated insulin processing with resulting accumulation of misfolded insulin and ER stress. The
impact of these studies will be a mechanistic characterization of the role of low, but environmentally realistic
concentrations of Cd in the development of type 2 diabetes mellitus.

## Key facts

- **NIH application ID:** 10167709
- **Project number:** 5R01ES027011-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Malek El Muayed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,910
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167709

## Citation

> US National Institutes of Health, RePORTER application 10167709, Mechanisms of Cadmium Induced Dysglycemia and Type 2 Diabetes Mellitus (5R01ES027011-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167709. Licensed CC0.

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