type 2 diabetes Archives - Sanford Burnham Prebys
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Scientists discover an early sign of type 2 diabetes: Misfolded proinsulin

AuthorMonica May
Date

March 19, 2020

The findings could lead to tests or treatments that help prevent type 2 diabetes.

Misfolded proinsulin—a protein the body normally processes into insulin—is an early sign of type 2 diabetes, according to a study by scientists at Sanford Burnham Prebys and the University of Michigan Medical School. The discovery, published in eLife, could lead to tests or treatments that help prevent people from developing type 2 diabetes.

“Understanding the molecular events that occur as prediabetes progresses to diabetes opens new avenues for us to detect or interrupt these processes,” says Randal Kaufman, PhD, director and professor in the Degenerative Diseases Program at Sanford Burnham Prebys and co-corresponding author of the study. “With this information, we can start to find interventions that might spare millions of people from a serious, lifelong condition.”

More than one in three Americans, or approximately 88 million people, have prediabetes—which is characterized by elevated blood sugar. If left untreated, within four years nearly 40% of people with prediabetes develop type 2 diabetes, which occurs when the body doesn’t use insulin properly. In 2017, the cost of treating diabetes exceeded $327 billion, according to the American Diabetes Association. Due to increasing obesity rates, the number of people with the condition—particularly children—is on the rise.

Identifying the molecular events that occur during progression from prediabetes to full-blown diabetes remains one of the most perplexing problems in diabetes research. In the study, the scientists set out to answer this question by tracking proinsulin folding in the beta cells of humans and mice that are healthy, prediabetic and diabetic.

These studies revealed that instead of undergoing its normal folding process, proinsulin proteins were abnormally linked to each other. Levels of the abnormal proinsulin accumulated as prediabetes progressed to type 2 diabetes. Obese mice in the earliest stages of diabetes had the highest levels of abnormal proinsulin in their beta cells.

“Proinsulin misfolding is the earliest known event that may contribute to the progression from prediabetes to diabetes,” says Kaufman. “Together, these studies show that abnormally linked proinsulin holds promise as a potential measure of how close someone may be to developing type 2 diabetes.”

Now, the researchers are set to uncover more details about this process, such as the proteins that interact with the misfolded proinsulin.

“Understanding the fundamental molecular events that lead to type 2 diabetes is critical as the number of people with prediabetes continues to rise,” says Kaufman. “If we don’t find preventive measures, we will soon have a diabetes epidemic.”


The study’s first author is Anoop Arunagiri, PhD; and the study’s senior author is Peter Arvan, both of the University of Michigan Medical School.

Additional authors include Leena Haataja and Fawnnie Pamenan of the University of Michigan Medical School; Ming Liu of the University of Michigan Medical School and Tianjin Medical University in China; Anita Pottekat and Pamela Itkin-Ansari of Sanford Burnham Prebys; Soohyun Kim of Konkuk University in South Korea; Lori M. Zeltser of Columbia University; Adrienne W. Paton and James C. Paton of the University of Adelaide in Australia; and Billy Tsai of the University of Michigan.

The study’s DOI is 10.7554/eLife.44532.

This work was supported by the National Institutes of Health (R01DK111174, R24DK110973 and R01DK48280) and the Juvenile Diabetes Research Foundation International (2-SRA-2018-539-A-B).

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Long-term exercise makes fat better at burning calories, but doesn’t turn it brown

AuthorJessica Moore
Date

November 15, 2016

Brown fat is good, white fat bad. That’s the impression given by recent metabolism research focused on how to make white fat, which stores energy, more like the rarer brown fat, which burns energy. However, a new study from the Florida Hospital Translational Research Institute for Metabolism and Diabetes (TRI-MD), an affiliate of Sanford Burnham Prebys Medical Discovery Institute (SBP), suggests that with regular exercise even white fat can be cajoled into burning more calories.

“Our findings reveal that even though exercise doesn’t turn white fat ‘beige’—that is, make some of it behave similarly to brown fat—it still has beneficial effects on metabolism in that tissue,” said Lauren M. Sparks, PhD, adjunct professor in the Integrative Metabolism Program at SBP in Lake Nona and an investigator at the TRI-MD. She led the research, recently published in the journal Obesity.

Prior to this investigation, not much was known about how exercise shapes the way human fat cells burn energy. One study suggested that endurance training does not change metabolism in white fat, but the experiments only assessed markers of ‘browning’. Sparks’ team aimed to examine the question more comprehensively by looking not only at browning markers, but also heat generation and the means by which most cells use energy—oxidizing fuels in mitochondria.

The researchers, including SBP’s Steven R. Smith, MD, scientific director of the TRI-MD, compared the abdominal fat of people who work out at least four hours per week at moderate to vigorous intensity to that of sedentary individuals. The levels of mitochondrial oxidation markers were higher in the fat of active people compared with the inactive group, the scientists found, However, markers of heat generation and conversion to ‘beige’ fat were similar between the groups.

“This work highlights the importance of studying metabolism in humans,” Smith said. “Because exercise training in rodents does cause white fat to burn calories as heat, these animals may not be ideal models for answering these kinds of questions.”

“Understanding the effects of exercise on metabolism at the molecular level is critical,” Sparks said. “It connects the dots between physical activity and disease, and it could help refine exercise programs that help people with metabolic problems such as type 2 diabetes and obesity get healthier.”

The paper is available online here.

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How your organs ‘taste’ sugar

Authorjmoore
Date

April 18, 2016

You might be surprised to learn that the sensors for sweet-tasting molecules aren’t located only on your tongue—they’re also found in the gut, pancreas, fat tissue, and muscle. And new research from the laboratory of George Kyriazis, PhD, assistant professor in the Integrative Metabolism Program at Lake Nona, indicates just how important these sweet taste receptors are in regulating metabolism. Continue reading “How your organs ‘taste’ sugar”

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Generating good fat by pushing the right buttons

Authorjmoore
Date

March 30, 2016

Researchers at SBP have identified a protein complex that is required for conversion of “bad” white fat to “good” brown fat. The findings, published in the Journal of Clinical Investigation, could help treat metabolic disorders such as obesity. Continue reading “Generating good fat by pushing the right buttons”

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New links between heart hormones, obesity, and diabetes

AuthorGuest Blogger
Date

February 17, 2016

New research from SBP’s Sheila Collins, PhD, and Richard Pratley, MD, has revealed an important relationship between proteins secreted by the heart and obesity, glucose intolerance, and insulin resistance. The findings, published in Obesity, offer a new approach to treating metabolic disorders, including type 2 diabetes, by targeting the pathway that controls the proteins’ concentration in the blood. Continue reading “New links between heart hormones, obesity, and diabetes”

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SBP’s Sheila Collins’ diabetes research featured in Orlando Sentinel

Authorsgammon
Date

December 21, 2015

“Obesity has reached epidemic proportions in the United States. Over 60 percent of the population can be classified as overweight or obese, placing them at risk for a large number of chronic diseases, including insulin resistance, cardiovascular disease, and type 2 diabetes,” says Sheila Collins, PhD, professor at SBP’s Lake Nona campus.

“There is a critical need for novel approaches to treating obesity—in particular, agents acting to increase energy expenditure would be valuable.”

Read the article in the Orlando Sentinel by Naseem S. Miller about how Collins is studying hormones produced by the heart to prevent obesity and possibly the myriad of disorders that come with it.

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Protecting pancreatic cells from stress could hold promise for treating diabetes

Authorsgammon
Date

April 21, 2015

 

Type 2 diabetes is a chronic disease that affects about eight percent of adults worldwide, significantly increasing the risk of heart disease and stroke. This disease interferes with the body’s ability to make or use a hormone called insulin, which is produced by beta cells in the pancreas. These cells eventually fail in many patients with type 2 diabetes, making insulin replacement therapy a necessity for survival. However, this treatment is imprecise, onerous and often promotes weight gain, highlighting the strong need for better treatment options. Continue reading “Protecting pancreatic cells from stress could hold promise for treating diabetes”

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Ketogenesis prevents fatty liver disease

Authorsgammon
Date

January 12, 2015

A new study, published in the Journal of Clinical Investigation, suggests that ketogenesis may prevent non-alcoholic fatty liver disease (NAFLD). NAFLD is term used to describe the accumulation of fat in the liver of people who drink little or no alcohol. It affects approximately one billion individuals worldwide, has become a leading cause of cirrhosis, and increases the risk of cardiovascular disease, including heart attacks and stroke. Continue reading “Ketogenesis prevents fatty liver disease”

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Exercise following bariatric surgery provides health benefits

Authorsgammon
Date

December 1, 2014

A new study by researchers at the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI-MD) in Orlando, Fla., shows that patients who moderately exercise after bariatric surgery (weight-loss surgery) gain additional health improvements in glucose metabolism and cardiorespiratory fitness compared to patients who lead a sedentary lifestyle after surgery. The findings confirm the physiological and potential clinical benefits of adding an exercise regime following weight-loss surgery. Continue reading “Exercise following bariatric surgery provides health benefits”