Role of mTORC1 in the progression to type 2 diabetes mellitus

Speaker: Carlos Guillén
Institution: Department of Biochemistry and Molecular Biology. School of Pharmacy

Place: Jerónimo Forteza conference room, CIPF

Abstract: Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial disease which is characterised by insulin resistance and the appearance of hyperinsulinemia during the first stages of the disease. As a consequence, pancreatic β cells are overwhelmed by its increased
capacity to produce and secrete more insulin, which is known as the pre-diabetic stage. Under this compensatory situation that occurs in β cells during the progression to T2DM, mTORC1 signalling pathway is one of the key regulators of pancreatic cell mass. In addition, there is a
chronic activation of mTORC1 signaling pathway, which induces aging and acts as an endogenous inhibitor of autophagy. Moreover, under this situation, pancreatic β cells start to accumulate amylin protein (IAPP) in aggregates, and this accumulation contributes as well to the  ailure of autophagy, damaging different organelles such as plasma membrane, endoplasmic reticulum, mitochondria, and others. Autophagy is involved in the recycling of cellular components for energy generation under nutrient deprivation, and serves as a complementary  egradation system to the ubiquitin-proteasome pathway. Autophagy represents a protective mechanism for different cell types, including pancreatic β cells, and potentiates β cell survival across the progression to T2DM. In summary, the chronic overactivation of mTORC1  ignaling pathway in β islets in a prediabetic situation, make these cells more prone to trigger apoptosis upon several cellular stressors and facilitates the progression from prediabetes to type 2 diabetes status.

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