News & Research

    University of Alabama at Birmingham, Birmingham, Alabama

Identification of a TXNIP-regulated microRNA involved in insulin production

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Islet Biology, Islet Biology\Beta Cell Transcription Regulation, Islet Biology\Metabolic Regulation, Islet Biology\Signal Transduction

Type of Grant: Basic Science

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

Diabetes has become a major public health issue and the epidemic continues to grow such that 1 in 3 Americans may have diabetes by 2050. While a number of therapies are available, they can significantly impact life quality, i.e. multiple daily insulin injections and often cannot prevent complications. Diabetes is characterized by insulin resistance, inadequate production of insulin by pancreatic beta cells and ultimately beta cell loss.

Recently, the Shalev laboratory has identified a novel target (TXNIP) to halt beta cell death and by inhibiting TXNIP was able to rescue mice from type 1 and type 2 diabetes. However, the role of TXNIP in beta cell function remained unknown. Surprisingly, Shalev now found that TXNIP also regulates another factor (encoded by which was previously considered "junk DNA") and this factor controls human insulin production. Interestingly, beta cell expression of this factor is abnormal in diabetes suggesting that it might be involved in the inadequate insulin production associated with this disease.

The aims of the proposed studies are therefore to obtain a better understanding of this novel pathway and the Shalev lab will use state-of-the-art molecular biology, mouse models and human beta cells to gain this crucial insight. The results of these studies will help identify novel therapeutic targets to enhance not only beta cell survival, but also the patient's own natural insulin production, which would improve blood glucose control, delay diabetes progression, reduce or eliminate the need for daily insulin injections and improve quality of life for patients with diabetes.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

The project covers novel mechanisms controlling the body's own insulin production and pancreatic beta cell biology.

Diabetes is characterized by insulin resistance, inadequate production of insulin by pancreatic beta cells and ultimately beta cell loss. Recently, we have identified a novel target (TXNIP) that halts beta cell death and by inhibiting TXNIP were able to rescue mice from type 1 and type 2 diabetes. However, the role of TXNIP in beta cell function remained unknown. Surprisingly, we now found that TXNIP also regulates another factor (encoded by which was previously considered "junk DNA") and this factor controls human insulin production. Interestingly, beta cell expression of this factor is abnormal in diabetes suggesting that it might be involved in the inadequate insulin production associated with this disease. We will use state-of-the-art molecular biology, mouse models and human beta cells to gain a better understanding of this novel pathway. The project will therefore help identify novel therapeutic targets to enhance not only beta cell survival, but also the patient's own natural insulin production, which would improve blood glucose control, prevent or delay diabetes progression and ultimately treat or even cure diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

The studies will help identify novel treatment approaches that enhance the body's own beta cell mass and function and natural insulin production. As such these therapies would facilitate blood glucose control, reduce or eliminate the need for daily insulin injections and thereby improve quality of life while preventing diabetes progression.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

I have been involved in diabetes research since Medical School and as a physician-scientist seeing patients with diabetes has served as a constant reminder that better treatment approaches are needed. I have therefore dedicated my career to finding better therapies for diabetes. For over 10 years my laboratory has focused on beta cell biology and this award is crucial for our continued research efforts and allowing us to follow-up on our newly discovered lead.

In what direction do you see the future of diabetes research going?

I believe that by obtaining a better understanding of beta cell biology, diabetes researchers will be able to device novel therapies geared toward the preservation and promotion of the patient's own beta cell mass and function. Such an approach would not require any invasive measures and yet provide optimal glucose control and prevent diabetes complications.