The Burnham buzz

November 16, 2009

New antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and other pesky bacteria. Andrei Osterman and collaborators have used comparisons of bacterial genomes to identify new targets for antibiotics and produced first-generation chemical inhibitors of a class of bacterial enzymes, called NadDs (nicotinate mononucleotide adenylyltransferases). Described in a recent article in Chemistry & Biology (Cell Press), the team, led by Dr. Osterman, has provided proof of concept for a novel class of antibiotics that could address the problem of antibiotic resistance in MRSA and other types of drug resistant bacteria. It is estimated that within the next one to two decades most antibiotics currently available will be useless due to the emergence of drug resistant strains.

Medical device for juvenile diabetes reaches key milestone on path to clinic. Patients currently receiving islet transplantation therapy for diabetes must undergo lifelong immunosuppression, rendering them more prone to infections and cancer. The idea of encapsulating the insulin-producing cells to hide them from the immune system has been popular for some years, but it has not been applied with much success. Recently Dr. Pamela Itkin-Ansari's team demonstrated that an encapsulation device protected cells from both allograft and autoimmune rejection in rodents, thus allowing this encapsulation therapy to successfully treat diabetes in the absence of immunosuppression. There are, however, differences between rodent and human immune systems. Therefore, as an important step toward clinical trials, Dr. Itkin-Ansari and colleagues have established that the device also provides immunoprotection in primates in an article recently published in Transplantation. With positive data in primates, the next step will be human clinical trials for juvenile diabetes.

Oxidants help cancers metastasize. Dr. Sara A. Courtneidge and colleagues have discovered that reactive oxygen species, such as superoxide and hydrogen peroxide, play a key role in forming invadopodia, cellular protrusions found on metastatic cancer cells. Invadopodia facilitate cancer cell migration by breaking down the extracellular matrix that normally keeps cells in place. In previous research, Dr. Courtneidge discovered that proteins called Tks4 and Tks5 are crucial for invadopodia formation. Now the Courtneidge laboratory has shown that antioxidants caused a marked reduction in invadopodia formation and invasive behavior. The findings also implicated enzymes called NADPH oxidases in the production of reactive oxygen. In collaborative studies with Dr. Gary Bokoch of The Scripps Research Institute, the Courtneidge laboratory has also found that Tks4 and Tks5 are part of a complex of proteins that allow the NADPH oxidases to function. With the discovery of reactive oxygen's role in invadopodia formation, researchers have additional possibilities for drug intervention. Future research and drug development will focus on inhibiting NADPH oxidase activity and limiting invadopodia formation to prevent cancer cell migration. These studies were published in September in the journal Science Signaling.

Complex sugar molecules (glycans) act as tumor suppressors. A team led by Dr. Minoru Fukuda discovered that specialized complex sugar molecules (glycans) that anchor cells in place act as tumor suppressors in breast and prostate cancers. These glycans play a critical role in cell adhesion in normal cells, and the Fukuda team found that the decrease or loss of these complex sugar molecules leads to increased cell migration by invasive cancer cells and metastasis. An increase in expression of the enzyme that produces these glycans, β3GnT1, resulted in a significant reduction in tumor activity. The study, which was published in the journal Proceedings of the National Academy of Sciences, provides a new understanding of the role that complex glycans play in cancer and could lead to new directions in the development of therapeutics.

Using stem cells therapeutically. In two recent papers in the journal Stem Cells, Dr. Evan Snyder and his team demonstrated the multifaceted therapeutic actions of neural stem cells in neurological diseases. Extending previously published work, the Snyder team showed that mice with a hereditary neurological disease could be rescued with stem cell transplants even when administered in the later stages of this disease, after symptoms have developed, to help lessen the disease's severity. This observation is important because most patients actually come to clinical attention after the disease has already become manifest. The stem cells were shown to have multifaceted actions in this mouse model, ranging from cell replacement to enzyme replacement and anti-inflammatory effects. Importantly, it was demonstrated that MRI can be used to "watch" the stem cells migrate to the regions of the brain where the pathology resides. In its second publication in Stem Cells, Dr. Snyder's team demonstrated that by altering the "pathological niche" - i.e., the area where transplanted stem cells and abnormal host cells interact - one can enhance the degree to which stem cells will reverse pathology, even when the disease is well-established. In this latter situation, the disease being tested was Parkinson's disease in aged adult mice. The therapeutic "cross-talk" between stem cells and host cells was facilitated by experimentally altering a component of the extracellular matrix. This paper illustrates some of the ways that the efficacy of stem cell transplantation therapy can be improved toward developing novel paradigms in regenerative medicine.

New insights into the development of "angry fat." It is well known that as fat (adipose) tissue expands with obesity, the fat cells become dysfunctional, elaborating factors that cause inflammation in other tissues leading to insulin resistance and diabetes. The mechanisms whereby the engorged fat cells become dysfunctional are unknown. Dr. Steven R. Smith (recently recruited BIMR Professor, Diabetes and Obesity Research Center) and colleagues have discovered a potential mechanism whereby fat cells become dysfunctional. Using novel techniques to measure oxygen levels in human adipose tissue, Smith and colleagues reported in the journal Diabetes that the vascular supply of fat does not keep pace with the expansion associated with the obese state. The relative reduction in blood supply was associated with increased elaboration of adipocytokines, the mediators of inflammation that contribute to the development of diabetes. This discovery identifies fat tissue blood vessel supply as a potential new target for development of drugs aimed at disconnecting obesity with the development of diabetes.

Sanford-Burnham Prebys Medical Discovery Institute

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to