Fractalkine circulates in bloodstream and stimulates insulin secretion, researchers find.

Jerrold Olefsky, UC San Diego

Researchers at the UC San Diego School of Medicine have identified a previously unknown biological mechanism involved in the regulation of pancreatic islet beta cells, whose role is to produce and release insulin. The discovery suggests a new therapeutic target for treating dysfunctional beta cells and type 2 diabetes, a disease affecting more than 25 million Americans.

Writing in the April 11 issue of Cell, Jerrold M. Olefsky, M.D., associate dean for scientific affairs and distinguished professor of medicine, and colleagues say a transmembrane binding protein called fractalkine, which typically mediates cell-to-cell adhesion though its receptor, CX3CR1, can also be released from cells to circulate in the blood and stimulate insulin secretion.

“Our discovery of fractalkine’s role in beta cells is novel and has never been talked about in prior literature,” said Olefsky. More importantly, the research highlights fractalkine’s apparently vital role in normal, healthy beta cell function. In mouse models and in cultured human islets, the researchers found administering the protein stimulated insulin secretion and improved glucose tolerance, both key factors in diabetes.  In contrast, fractalkine had no effect in mice or islets when the fractalkine receptor was deleted.

“Whether or not decreased fractalkine or impaired fractalkine signaling are causes of decreased beta cell function in diabetes is unknown,” said Olefsky. “What we do know, without doubt, is that administration of fractalkine improves or restores insulin secretion in all of the mouse models we have examined, as well as in human islet cells.”

Olefsky said fractalkine or a protein analog could prove “a potential treatment to improve insulin secretion in type 2 diabetic patients. It might also improve beta cell function or beta cell health, beyond simply increasing insulin secretion, since fractalkine prevents beta cell apoptosis (cell death) and promotes the beta cell differentiation program.

“If successfully developed, this could be an important new complement to the therapeutic arsenal we use in type 2 diabetes,” Olefsky continued. “It is not likely to ‘cure’ diabetes, but it would certainly do a good job at providing glycemic control.”

Read more

The abnormalities may be associated with increased risk of neuroendocrine tumors.

Peter Butler, UCLA

Individuals who had taken a type of drug commonly used to treat Type 2 diabetes showed abnormalities in the pancreas, including cell proliferation, that may be associated with an increased risk of neuroendocrine tumors, according to a new study by researchers from UCLA and the University of Florida. Their findings were published online March 22 in the journal Diabetes.

The researchers, from the Larry L. Hillblom Islet Research Center at UCLA and the Diabetes Center at the University of Florida, found that cell mass was increased approximately 40 percent in the pancreases of deceased organ donors who had Type 2 diabetes and who had been treated with incretin therapy. This widely used type of treatment takes advantage of the action of a gut hormone known as glucagon-like peptide 1 (GLP-1) to lower blood sugar in the body.

Although there have been conflicting reports on the effects of the incretin class of drugs on the pancreas in animal studies, this is the first study to note such changes in the human pancreas. The research was made possible by a unique research consortium called nPOD (Network for Pancreatic Organ Donors with Diabetes), led by Dr. Mark Atkinson, a professor of pathology and pediatrics at the University of Florida. The network, which is funded by the Juvenile Diabetes Research Foundation, obtains pancreases from deceased organ donors, with permission of their next of kin, to better understand diabetes by investigating tissues of those with the disease.

“There is an increasing appreciation that animal studies do not always predict findings in humans,” said Dr. Peter Butler, director of UCLA’s Hillblom Islet Research Center and chief of the endocrinology, diabetes and hypertension unit. “The nPOD program is therefore a very precious resource.”

Read more

Study suggests need for additional support when leaving pediatric providers.

Debra Lotstein, UCLA

Type 1 diabetes is a condition in which the body does not produce insulin and cannot convert sugar, starches and other food into energy. Generally diagnosed during childhood or adolescence, the disease requires lifelong access to medical care and intensive daily self-management.

As children with Type 1 diabetes grow into young adults, they must leave their pediatric health care providers for adult providers. But the timing of this process and its impact on the young people’s health had not been fully explored.

In a new study published in the April issue of the journal Pediatrics and currently available online, UCLA researchers found that young people with Type 1 diabetes who had transitioned from pediatric to adult care were 2.5 times more likely to have chronically high blood glucose levels, putting them at higher risk for heart attacks, strokes, blindness and kidney failure later in life.

The estimated median age of patients when this transition occurred was 20.1 years, the researchers said, and 77 percent had left pediatric care by age 21.

The findings suggest that young adults need additional support and guidance when leaving their pediatric providers to avoid the risk of poor diabetes control.

Read more

UCLA nursing professor co-authors World Health Organization report.

Linda Sarna, UCLA

Nurses and midwives can play a critical role in lessening people’s risk of cardiovascular diseases, cancers, chronic respiratory disease and diabetes, according to a groundbreaking new report issued by the World Health Organization and co-authored by a UCLA nursing professor.

These four non-communicable disease types account for a combined 60 percent of all deaths worldwide.

“The global burden of non-communicable diseases is already high and continues to grow in all regions of the world,” said Linda Sarna, a professor at the UCLA School of Nursing and co-author of the report. “Nurses and midwives have the expertise to help individuals and communities improve health outcomes.”

Sarna points out that since nurses and midwives make up more than 50 percent of all health care providers in most countries, they are the logical candidates to affect lifestyle changes among patients and increase health awareness. Worldwide, there are more than 19 million nurses and midwives, she said.

The 38-page report issued by the WHO highlights evidence-based, value-added nursing interventions that have been shown to reduce such risk factors as tobacco use, alcohol dependence, physical inactivity and unhealthy diets.

“The examples contained in the report are proven activities that nurses can start doing today to make a meaningful impact with their patients and in their community,” Sarna said. “Many of the interventions have been proven to reduce costs and improve the quality of care.”

Read more

Agreement with UC Merced professor an important show of faith.

Rudy Ortiz, UC Merced

UC Merced biology professor Rudy Ortiz is furthering his innovative research into diabetes with support from a major pharmaceutical company.

Ortiz’ work, developing new applications for medicines used to treat the effects of insulin resistance, has been funded by Amylin Pharmaceuticals LLC, a wholly owned subsidiary of Bristol-Myers Squibb Co., to the tune of $192,000 over two years.

Such funding agreements are common on other UC campuses and in comparable research institutions, and this agreement at UC Merced constitutes an important show of faith from the pharmaceutical industry in the young campus’s research capabilities.

“We will evaluate a drug that is traditionally used to address gluco-regulatory imbalance —the hallmark of diabetes — on a different aspect of diabetes,” Ortiz said. “This drug has also been proposed as a potential alternative to alleviate the hypertension associated with diabetes by improving the kidneys’ ability to regulate sodium.”

Read more

UCSF clinic is steps away from the future UCSF Benioff Children’s Hospital.

Kendall Layous, and her mother Shonda, make drawings that are used as table-top covers, part of an art therapy program at the UCSF Madison Clinic for Pediatric Diabetes.

In the two years since the Madison Clinic for Pediatric Diabetes was established through an anonymous, $10 million gift, it has evolved into a state-of-the-art facility with innovative programs and a new home on the Mission Bay campus.

The Madison Clinic at Mission Bay, now located steps away from the future UCSF Benioff Children’s Hospital, offers comprehensive care for children and young adults with diabetes, with an emphasis on patient education, empowerment and the use of advanced technologies. It also has a commitment to advancing research in the management of diabetes in children.

A multidisciplinary team – including endocrinologists, clinical psychologists, nurses, diabetes educators, social workers, dietitians, and administrative staff – ensures patients’ varying needs are met.

“I don’t really manage diabetes. The parents do it all day, every day,” said Saleh Adi, M.D., medical director of the Madison Clinic and a pediatric endocrinologist. “Our job is to teach them how and provide them with the tools they need, and to be there for support and feedback whenever they need it.”

Shonda and Brad Layous know firsthand how much is required of parents with diabetic children. Their daughter Kendall was diagnosed with type 1 diabetes in April 2012, two days after her second birthday.

“Having a child with a serious health condition takes its toll on the entire family, so a bright spot in this emotional year for us was finding the Madison Clinic,” said Shonda Layous. “Our family knows that we are in the best care possible at the UCSF Madison Clinic, and its amazing staff and wonderful space give us comfort and confidence that we will partner with them for life to best manage her disease.”

There currently are 25.8 million children and adults in the United States, or 8.3 percent of the population, living with diabetes, according to the American Diabetes Association. One in every 400 children and adolescents younger than age 20 has the chronic disease, which is characterized by the body’s inability to regulate blood glucose, or blood sugar, levels.

With the incidence of both type 1 and type 2 diabetes in children on the rise, it is increasingly important to have skilled teams of diabetes health care providers who specialize in treating young people.

Read more

Recon 2 is most comprehensive virtual reconstruction of human metabolic network to date.

Researchers liken Recon 2 to Google mapping for its ability to merge complex details into a single, interactive map.

Building on earlier pioneering work by researchers at the University of California, San Diego, an international consortium of university researchers has produced the most comprehensive virtual reconstruction of human metabolism to date. Scientists could use the model, known as Recon 2, to identify causes of and new treatments for diseases like cancer, diabetes and even psychiatric and neurodegenerative disorders. Each person’s metabolism, which represents the conversion of food sources into energy and the assembly of molecules, is determined by genetics, environment and nutrition.

The researchers presented Recon 2 in a paper published online March 3 in the journal Nature Biotechnology.

Doctors have long recognized the importance of metabolic imbalances as an underlying cause of disease, but scientists have been ramping up their research on the connection as a result of compelling evidence enabled by the Human Genome Project and advances in systems biology, which leverages the power of high-powered computing to build vast interactive databases of biological information.

“Recon 2 allows biomedical researchers to study the human metabolic network with more precision than was ever previously possible. This is essential to understanding where and how specific metabolic pathways go off track to create disease,” said Bernhard Palsson, Galletti Professor of Bioengineering at UC San Diego Jacobs School of Engineering.

“It’s like having the coordinates of all the cars in town, but no street map. Without this tool, we don’t know why people are moving the way they are,” said Palsson.

He likened Recon 2 to Google mapping for its ability to merge complex details into a single, interactive map. For example, researchers looking at how metabolism sets the stage for cancerous tumor growth could zoom in on the “map” for finely detailed images of individual metabolic reactions or zoom out to look at patterns and relationships among pathways or different sectors of metabolism. This is not unlike how you can get a street view of a single house or zoom out to see how the house fits into the whole neighborhood, city, state, country and globe.  And just as Google maps brings together a broad set of data – such as images, addresses, streets and traffic flow – into an easily navigated tool, Recon 2 pulls together a vast compendium of data from published literature and existing models of metabolic processes.

Read more

Results provide evidence that not all calories are equal from a diabetes-risk standpoint.

Sanjay Basu, UC San Francisco

Does eating too much sugar cause diabetes?

For years, scientists have said “not exactly.” Eating too much of any food, including sugar, can cause you to gain weight; it’s the resulting obesity that predisposes people to diabetes, according to the prevailing theory.

But now the results of a large epidemiological study conducted at UC San Francisco suggest that sugar may also have a direct, independent link to diabetes.

Researchers examined data on global sugar availability and diabetes rates from 175 countries over the past decade. After accounting for obesity and a large array of other factors, the researchers found that increased sugar in a population’s food supply was linked to higher diabetes rates, independent of obesity rates. Their study was published Feb. 27 in PLOS ONE.

The study provides the first large-scale, population-based evidence for the idea that not all calories are equal from a diabetes-risk standpoint.

Robert Lustig, UC San Francisco

“It was quite a surprise,” said Sanjay Basu, M.D., Ph.D., an assistant professor of medicine at the Stanford Prevention Research Center and the study’s lead author. The research was conducted while Basu was a medical resident at UCSF and working with Robert Lustig, M.D., a pediatric endocrinologist at UCSF Benioff Children’s Hospital and the paper’s senior author.

“We’re not diminishing the importance of obesity at all, but these data suggest that at a population level there are additional factors that contribute to diabetes risk besides obesity and total calorie intake, and that sugar appears to play a prominent role.”

Specifically, more sugar was correlated with more diabetes: For every additional 150 calories of sugar available per person per day, the prevalence of diabetes in the population rose 1 percent, even after controlling for obesity, physical activity, other types of calories and a number of economic and social variables. A 12-ounce can of soda contains about 150 calories of sugar. In contrast, an additional 150 calories of any type caused only a 0.1 percent increase in the population’s diabetes rate.

Read more

Related links:

• It’s the sugar, folks (New York Times)
• Availability of sugar influences rate of diabetes, study says (Los Angeles Times)
• More sugar, more diabetes (KQED)

UC Davis researcher will focus on blocking the pancreatic hormone amylin.

Florin Despa, UC Davis

A UC Davis pharmacologist has been awarded a two-year, $95,000 Innovation Award from the American Diabetes Association to find out if blocking the pancreatic hormone amylin can reduce diabetic heart failure.

The researcher — Florin Despa — previously found that amylin accumulates in strings of proteins called oligomers in the heart tissue of patients with heart disease and type 2 diabetes or obesity.

“We now want to determine if limiting accumulation of oligomerized amylin in cardiac tissue can delay or even prevent the development of diabetic heart failure,” said Despa, an assistant professor of pharmacology in the UC Davis School of Medicine. “This is a priority for my lab, because heart failure is the number-one killer for people with diabetes.”

In healthy people, amylin circulates in the blood together with insulin — the hormone that controls carbohydrate and fat metabolism — and principally regulates gastric fluxes and the sensation of satiety.

In previous experiments, Despa found widespread amylin deposition in tissue from failing hearts of patients with type 2 diabetes or obesity. Those who were overweight but not obese had some, but not extensive, amylin accumulation, and there was little or none in the heart tissue of lean or non-diabetic people. These studies suggested that cardiac accumulation of the hormone has a role in advancing heart failure for those who are diabetic or obese.

Despa will use the new funding to find out if signaling molecules that have anti-aggregation properties — such as plasmin and eicosanoids — can limit amylin accumulation and its destructive heart-health effects in rats.

“If successful, this project may lead to new therapeutic targets for cardioprotection for those with diabetes,” said Despa.

The American Diabetes Association funds research that accelerates progress toward improved treatments and a cure for diabetes. The program emphasizes innovative and novel projects, along with funding opportunities for early-career researchers. For more information, visit www.diabetes.org.

View original article

San Diego Supercomputer Center to host infrastructure.

Researchers at UC San Diego have been awarded a new National Institutes of Health (NIH) grant to expand and enhance a cyberinfrastructure designed to provide scientists with easily accessible, Web-based resources to help fight diabetes and metabolic diseases.

The grant, awarded through the university’s Center for Research in Biological Systems (CRBS), will focus on establishing, coordinating, and making available large pools of datasets to researchers as part of a project to further develop the National Institute of Diabetes and Digestive and Kidney Diseases’ (NIDDK) Interconnectivity Network community and infrastructure.

About 25.8 million children and adults in the United States, or 8.3 percent of the population, have diabetes, according to the American Diabetes Association. Obesity has been cited as a contributing factor to approximately 100,000 to 400,000 deaths in the U.S. each year.

Established in 2010, a prototype of the current system called dkCOIN was initially created to explore requirements for information sharing between four NIDDK-supported consortia, including the Nuclear Receptor Signaling Atlas (NURSA), the Beta Cell Biology Consortium (BCBC), the Mouse Metabolic Phenotyping Centers (MMPC), and the Diabetic Complications Consortium (DCC).

The new NIH grant will allow UC San Diego researchers to expand the data federation and develop and enhance a user-friendly Web portal that will seamlessly integrate information, resources, and data held by NIDDK-related research groups, with the goal of providing a valuable resource for NIDDK investigators.

Read more

Institute will speed efforts to deliver new drugs, technologies, procedures to patients.

UC San Diego leaders, philanthropists and community members gathered Thursday to celebrate the official start of construction on the Altman Clinical and Translational Research Institute (CTRI) building, and to show gratitude to the family whose generosity has helped to make the state-of-the-art building possible.

Set to open in 2016, the Altman CTRI will accelerate efforts to deliver new drugs, technologies and procedures to patients who need them most, speakers said. Its location, footsteps from many clinical facilities on the UC San Diego Health System campus in La Jolla, makes it one of only a handful of such centers in the nation.

“This is a building that is going to be a bridge to our future; where we are going to define new cures, where we are going to define how medicine should be practiced,” said Chancellor Pradeep K. Khosla.

The building is named for San Diego philanthropists and longtime residents Lisa and Steve Altman, who have pledged $10 million toward its construction. Steve Altman is vice chairman of Qualcomm Inc.; he and his wife, Lisa, have been generous patrons of many local and national charities.

The Altmans’ gift was inspired by the prevalence of type 1 diabetes in their family. Two of the Altmans’ three children have the disease, and multiple other family members have lived with diabetes since childhood. The Altman CTRI building will be the new home of the UC San Diego Pediatric Diabetes Research Center, and it will welcome patients taking part in clinical trials.

“Other than marrying my wife, Lisa, this was the biggest no-brainer thing for us to do in our lives,” Steve Altman said. “To get these kinds of capabilities here in San Diego, at such a fine institution with so much talent, and putting it all together, it’s something that’s clearly of great need.”

The Altmans were toasted by friend Rich Sulpizio, whose family made a leadership gift to name the Sulpizio Cardiovascular Center, which opened in 2011. Steve Altman and Rich Sulpizio have been longtime colleagues at Qualcomm. Steve Altman shared that he was delighted that the Altman CTRI would be connected to the Sulpizio Cardiovascular Center by a bridge – a lasting symbol of the connection between the two families.

Based on the idea that solving today’s complex medical challenges requires an innovative approach, the facility unites laboratory and clinical researchers with shared resources to support their work in space designed to encourage collaboration. The discoveries that will emerge will benefit patients everywhere.

“That’s what makes this the opportunity of a lifetime,” said UC San Diego Health System CEO Paul Viviano.

UC San Diego is uniquely positioned to host such a center because of its collaborative spirit, talented faculty and staff and its location in the midst of a high concentration of world-class public and private research institutions.

“A facility like this could not exist anywhere else in our region,” said Dr. David A. Brenner, vice chancellor for health sciences and dean of the UC San Diego School of Medicine. “In fact, there are only a handful of places across the nation where it could be successful. I feel lucky to live and work in such a place.”

Read more

UC Davis study deflates that notion.

People who are “apple-shaped” — with fat more concentrated around the abdomen — have long been considered more at risk for conditions such as heart disease and diabetes than those who are “pear-shaped” and carry weight more in the buttocks, hips and thighs.

But new research conducted at UC Davis Health System published in The Journal of Clinical Endocrinology and Metabolism provides further evidence that the protective benefits of having a pear-body shape may be more myth than reality. The journal article posted online today (Jan. 10) and will appear in the March print edition.

The UC Davis study found that fat stored in the buttock area — also known as gluteal adipose tissue — secretes abnormal levels of chemerin and omentin-1, proteins that can lead to inflammation and a prediabetic condition know as insulin resistance in individuals with early metabolic syndrome.

Metabolic syndrome refers to a group of risk factors that occur together, doubling the risk for heart disease and increasing the risk for diabetes at least five-fold. Risk factors include having a large waistline, low levels of high-density lipoproteins (HDL), or “good” cholesterol, high blood pressure as well as high fasting blood sugar ( insulin resistance) and high triglyceride levels. According to the Centers for Disease Control and Prevention, metabolic syndrome affects 35 percent of American adults over age 20.

“Fat in the abdomen has long been considered the most detrimental to health, and gluteal fat was thought to protect against diabetes, heart disease and metabolic syndrome,” said Ishwarlal Jialal, lead author of the study and a professor of pathology and laboratory medicine and of internal medicine at UC Davis. ”But our research helps to dispel the myth that gluteal fat is ‘innocent.’ It also suggests that abnormal protein levels may be an early indicator to identify those at risk for developing metabolic syndrome.”

The UC Davis team found that in individuals with early metabolic syndrome, gluteal fat secreted elevated levels of chemerin and low levels of omentin-1 — proteins that correlate with other factors known to increase the risk for heart disease and diabetes.  High chemerin levels, for example, correlated with high blood pressure, elevated levels of C-reactive protein (a sign of inflammation) and triglycerides, insulin resistance, and low levels of HDL cholesterol. Low omentin-1 levels correlated with high levels of triglycerides and blood glucose levels and low levels of HDL cholesterol.

“High chemerin levels correlated with four of the five characteristics of metabolic syndrome and may be a promising biomarker for metabolic syndrome,” said Jialal. “As it’s also an indicator of inflammation and insulin resistance, it could also emerge as part of a biomarker panel to define high-risk obesity states. The good news is that with weight loss, you can reduce chemerin levels along with the risk for metabolic syndrome.”

Read more