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ß-cell Dysfunction in Diabetes: Elucidating the Role of Islet-Associated Mesenchymal Cells

Objective

"Glucose homeostasis relies on tightly controlled release of insulin by pancreatic beta-cells. Diabetes, characterized by increased blood glucose levels, is a chronic disease now reaching epidemic proportions. The most common form of this disease is Type 2 diabetes (T2D), which was previously regarded as a disease of insulin resistance. However, work over the past decade
had shifted this paradigm by implicating beta-cell failure as a key factor in this disease. Despite major progress, the cellular and molecular basis of this T2D is far from being elucidated. Here, I present a novel pancreatic cell population, islet-associated mesenchymal cells (isMCs), which are with close contact to beta-cells in both human and mouse pancreata. My preliminary findings revealed that isMCs function to maintain beta-cells maturity and functionality. I therefore hypothesize that impaired isMCs function serve as an underlying cause for diabetes. To test this hypothesis, we will characterize the continuous requirement of isMCs for glucose homeostasis by their specific depletion in vivo. Next, we will link genes associated with T2D to isMCs function, by manipulating their expression and elucidating the effect on beta-cell function. Finally, we will investigate the source of diabetes prevalence found in pancreatic cancer and pancreatitis patients, by identifying how isMCs ability to maintain beta-cell function is affected in these diseases. To this end, we will use transgenic mouse models and culture systems to specifically manipulate cells and genes, and to study the resultant effect on beta-cell phenotype and glucose homeostasis. The implications of this work are far reaching as they will point to isMCs as a new player in glucose regulation, and as a contributor to beta-cell dysfunction in diabetes. Furthermore, the findings of this study will implicate isMCs a novel target for therapeutic approaches to diabetes, a currently unmet medical need."

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /medical and health sciences/clinical medicine/endocrinology/diabetes
  • /medical and health sciences/clinical medicine/oncology/cancer

Call for proposal

ERC-2013-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

TEL AVIV UNIVERSITY
Address
Ramat Aviv
69978 Tel Aviv
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 105 439,60
Principal investigator
Limor Landsman (Dr.)
Administrative Contact
Lea Pais (Ms.)

Beneficiaries (1)

TEL AVIV UNIVERSITY
Israel
EU contribution
€ 1 105 439,60
Address
Ramat Aviv
69978 Tel Aviv
Activity type
Higher or Secondary Education Establishments
Principal investigator
Limor Landsman (Dr.)
Administrative Contact
Lea Pais (Ms.)