Summary
Type 2 diabetes (T2D) has reached epidemic proportions, killing millions each year; however, our incomplete understanding of its etiology hinders the quest for a cure. T2D is caused by pancreatic β-cell failure and insulin resistance. Recent studies point to aberrant islet inflammation as a driver of diabetes. While inflammation is beneficial for insulin secretion during homeostasis, it may transform to harm β-cell function and impair the glucose response. How islet inflammation maintains glucose homeostasis and why it converts to being destructive remain largely open questions. Here, I introduce a novel physiological mechanism, pericyte-orchestrated islet inflammation (PIIN), which is disturbed by diabetes risk factors to cause β-cell failure. To establish its requirement for β-cell function, we will first define the role of PIIN in homeostasis. We will then determine how T2D environmental risks, such as obesity and aging, hamper pericyte cytokine production and transform islet inflammation to cause β-cell dysfunction. Lastly, we will link T2D genetic risk factors with aberrant PIIN. To this end, we will analyze human and mouse tissues and use transgenic models to manipulate cells and genes to define the effect of PIIN on β-cell function. Ultimately, our findings will provide a mechanism through which T2D risk factors induce β-cell failure and promote disease progression. The implications of this project are far-reaching, as they will introduce a novel cellular mechanism that integrates metabolic and genetic risks to cause diabetes. Furthermore, our findings will implicate PIIN as a novel target for new therapeutic approaches to diabetes.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101088870 |
| Start date: | 01-07-2023 |
| End date: | 30-06-2028 |
| Total budget - Public funding: | 2 000 000,00 Euro - 2 000 000,00 Euro |
Cordis data
Original description
Type 2 diabetes (T2D) has reached epidemic proportions, killing millions each year; however, our incomplete understanding of its etiology hinders the quest for a cure. T2D is caused by pancreatic β-cell failure and insulin resistance. Recent studies point to aberrant islet inflammation as a driver of diabetes. While inflammation is beneficial for insulin secretion during homeostasis, it may transform to harm β-cell function and impair the glucose response. How islet inflammation maintains glucose homeostasis and why it converts to being destructive remain largely open questions. Here, I introduce a novel physiological mechanism, pericyte-orchestrated islet inflammation (PIIN), which is disturbed by diabetes risk factors to cause β-cell failure. To establish its requirement for β-cell function, we will first define the role of PIIN in homeostasis. We will then determine how T2D environmental risks, such as obesity and aging, hamper pericyte cytokine production and transform islet inflammation to cause β-cell dysfunction. Lastly, we will link T2D genetic risk factors with aberrant PIIN. To this end, we will analyze human and mouse tissues and use transgenic models to manipulate cells and genes to define the effect of PIIN on β-cell function. Ultimately, our findings will provide a mechanism through which T2D risk factors induce β-cell failure and promote disease progression. The implications of this project are far-reaching, as they will introduce a novel cellular mechanism that integrates metabolic and genetic risks to cause diabetes. Furthermore, our findings will implicate PIIN as a novel target for new therapeutic approaches to diabetes.Status
SIGNEDCall topic
ERC-2022-COGUpdate Date
31-07-2023
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