H2020Индивидуална стипендия2018–2020

INSULYSOSOME · The role of CD63 in lysosomal degradation of insulin granules in pancreatic beta cells in T2D diabetes

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-11-01 → 2020-10-31
Финансиране от ЕС: 173 076 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Бета-клетките в панкреаса и ролята на протеина CD63 при разграждането на инсулиновите гранули се анализират в контекста на диабета тип 2. Разбирането на тези процеси помага за търсенето на нови терапевтични подходи за справяне с болестта.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

The role of CD63 in lysosomal degradation of insulin granules in pancreatic beta cells in T2D diabetes

Concerns about the global diabetes epidemic continue to grow. In 2019, it has been established that 463 million people live with Diabetes. According to the last predictions made by the international Diabetes Federation in 2030 this number should reach 578 million. This developments are very alarming as the number of actual cases surpasses above estimations. Sedentary life style and overnutrition, hallmarks of our modern society, account for this epidemic disease propagation. To maintain blood glucose at a normal level, the pancreatic β cell harbors an exemplary nutrient sensing machinery that is coupled to secretion of insulin. The pancreatic β cell mainly senses increasing glucose levels and secretes insulin that acts to promote the energy storage in different organs. Inversely, the β cell decreases insulin secretion to make available stored energy upon low glucose levels during fasting. Overnutrition conditions in combination with physical inactivity may trigger obesity and insulin resistance. To meet high insulin demands encountered in obese people, the pancreatic β cell will enhance its insulin secretory capacity. However, these compensatory mechanisms will eventually be overwhelmed culminating in β cell failure and full-blown type 2 diabetes (T2D). While huge research efforts have been intended to unravel and target molecular mechanisms behind T2D, the picture is still far from being complete. While mechanisms linking glucose sensing to release of insulin have been widely investigated, little is known about how nutrients impact on insulin granule generation and their destination in the cell. Hence, novel research insights leading to therapeutic approaches are highly demanded to prevent enormous health costs and negative consequences of our modern lifestyle. We have recently discovered a novel concept in which the newly-made insulin granules can be routed either for secretion in presence or for degradation in absence of nutrients. Moreover, we have discovered that routing insulin granules for degradation could be a hallmark of diabetic ß cells that may contribute to secretory dysfunction in T2D. Based on these findings, we have explored more fundamentally the role insulin granule degradation in ß cell function. It is essential to understand the molecular mechanisms behind the degradation of insulin in pancreatic ß cells and to address how this deregulation can promote progression of T2D.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The pancreatic β cell harbors an exemplary nutrient sensing machinery that is coupled to secretion of insulin. While mechanisms governing regulation of insulin secretion in response to nutrients were widely investigated, little is known about how nutrients impact on other basic cellular processes such as insulin granule turnover, autophagy and cellular growth, deregulation of all of which have been demonstrated to be involved in β cell failure in type 2 diabetes (T2D). T2D represents a major health burden accounting for a large part of exploding health costs world-wide. Restoring normal weight through exercise and decreased food consumption in principle is straight-forward to mitigate metabolic disturbances. However, changing the sedentary life style is very challenging for obese subjects and that at a late disease stage, β cell failure becomes irreversible. There is an emerging endeavor of the pharmaceutical industry to develop strategies targeting the β cell that go beyond improving insulin secretion. A prevailing concept in cell biology is that enhanced degradation of cellular components through autophagy can counteract energy depletion caused by shortage of environmental nutrients. My host laboratory recently discovered that β cells employ a very distinct and so far unknown mechanism to adapt to nutrient depletion. β cells induce specific degradation of newly formed insulin granules through lysosomes and suppress autophagy upon nutrient withdrawal. Insulin granule degradation allows for generation of intracellular nutrients and in the same time avoids release of these granules. Their preliminary results suggest that lysosomal insulin granule degradation is dramatically enhanced in β cells of diabetic islets from mice and humans. This increase is accompanied by a drop in autophagy, a known protective process in the β cell. My project will fortify that impaired lysosomal activity, insulin degradation and suppressed autophagy contribute to β cell failure in T2D.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE · Illkirch GraffenstadenКоординаторФранция