News & Research

    University of Texas Health Science Center San Antonio, San Antonio, Texas

Mechanism of impaired glucose metabolism in the preterm baboon model

General Research Subject: Insulin Resistance Pre Diabetes

Focus: Insulin Action\Signal Transduction, Integrated Physiology\Insulin Resistance, Integrated Physiology\Muscle

Type of Grant: Basic Science

Project Start Date: July 1, 2011

Project End Date: June 30, 2014

Research Description

High blood sugar is a common condition that affects premature infants. This condition has been linked to higher risk of developing other diseases such as blindness, brain bleeds and death. Human and animal studies suggest that tissues that usually respond well to insulin in older children (to maintain normal blood sugar) are not as responsive to insulin in premature infants.  The primary goal of this project is to investigate if the responses from those tissues to insulin mature with time after birth and evaluate those differences between those born prematurely and those born at term. If born prematurely, they may have prolonged difficulties responding to insulin in various tissues resulting in the high blood sugars that are seen in premature infants.  Additionally, a new medication that improves the responses of tissues to insulin will be tested to determine if these abnormalities improve and in turn, blood sugar will be maintained within normal levels. This medication is currently being tested to be used for the treatment of diabetes. Prematurity has been steadily increasing over the last decade and improving the health of this population is very important.  In addition, premature infants and infants who are born small have increased risks of developing type 2 diabetes, obesity and other adult diseases early in life. Therefore, understanding the insulin responses in tissues may lead to the utilization of newer therapies improving glucose control in newborns and decreasing their subsequent risk of 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?

People with diabetes, both type 1 and type 2, have insufficient numbers of the pancreatic beta cells that secrete insulin.  In adult mice (and, we believe also in humans, although it’s not yet known for sure), the largest source of new beta cells is proliferation of existing beta cells. Recent experiments in my laboratory have shown that a form of fat called free fatty acids, that circulates in the bloodstream in all people, can prevent beta cell proliferation. Intriguingly, increasing free fatty acid levels in mice causes a protein called p16, which blocks proliferation by halting the cell cycle, to be more abundant in islets. When we studied this phenomenon in beta cells growing in a dish, we found that p16 was required for free fatty acids to block proliferation. The experiments we will perform as part of this grant application will determine whether p16 is important for this process in mice. We will also perform experiments to verify that our findings in mice also apply to human beta cells. If our hypothesis is correct, this work will uncover an important new therapeutic target to restore pancreatic insulin secretion to prevent or treat diabetes.

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

In my opinion, a true “cure” for diabetes means restoration of pancreatic beta cell mass and function. This project aims to understand one reason why beta cell mass fails to expand in people who become diabetic. If successful, our research will identify a new therapeutic pathway that may eventually allow restoration of pancreatic insulin secretory capacity in people with diabetes.

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

This award has enormous meaning for me. As a practicing Endocrinologist, I see patients every week who struggle with diabetes, both with the seemingly impossible recommendations to change fundamental aspects of how they live, and with the threat and, in some cases, reality of acute and chronic diabetes complications. This ADA grant is my first independent research award. In today’s difficult funding climate, this award may mean the difference between success and failure as a diabetes researcher. The nature of this award, funded by small gifts from thousands of individuals with a personal stake in the future of diabetes research, gives me a strong sense of personal responsibility; I feel that a precious trust has been placed in me. I hope my efforts move the field of diabetes research forward in a meaningful way.

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

In the short term, I see improvements in therapy for diabetes, with closing the loop between glucose monitoring and insulin delivery. However, closed-loop insulin delivery will remain a highly specialized, labor intensive and expensive therapy that won’t be possible for all patients. My dream is to develop a true cure, meaning restoration of normal pancreatic glucose sensing and insulin secretion, which could be applied to all patients with prediabetes and diabetes.