Pesquisadores dos EUA descobrem possível 'cura' para diabetes tipo 1

Desativação de hormônio dispensaria injeções de insulina, dizem cientistas. Testes pré-clínicos foram feitos em camundongos.

Uma equipe do Centro Médico da Universidade do Sudoeste do Texas, nos Estados Unidos, sugere que a desativação de um hormônio pode ser suficiente para tratar diabetes tipo 1, uma doença autoimune - na qual o sistema de defesa ataca as células e tecidos do próprio corpo -, que faz as concentrações de açúcar no organismo ficarem muito altas. A descoberta será tema de edição de fevereiro da revista especializada "Diabetes".

Liderados por Roger Unger, professor da instituição e principal autor do artigo científico, os pesquisadores testaram a capacidade de camundongos, cobaias comuns em testes pré-clínicos, aproveitarem o açúcar presente no sangue, fruto da alimentação dos animais.

No caso dos diabéticos, essa ação do glucagon faz os níveis de glicemia aumentarem muito. Esse efeito seria compensado em pessoas saudáveis pela ação da insulina, responsável por permitir que o açúcar penetre nas células do corpo. Dentro delas, a glicose poderia ser imediatamente aproveitada para gerar energia ou armazenada. Mas para os pacientes com diabetes tipo 1, a produção de insulina não existe ou é seriamente comprometida.O truque foi alterar geneticamente os roedores para que produzissem quantidades menores de uma substância conhecida como glucagon, responsável por impedir que os níveis de glicose (açúcar) fiquem muito baixos.

Mas os pesquisadores norte-americanos acreditam que os resultados obtidos com os camundongos apontem que, caso os níveis de glucagon consigam ser controlados, a insulina se torna supérflua, já que os níveis de glicemia estariam normais, dispensando as injeções da substância para equilibrar a "balança" do açúcar no sangue.

Batalha de hormônios

A insulina deixa de existir em pacientes com diabetes tipo 1 pois o sistema de defesa do corpo ataca 90% ou mais das células beta, estruturas localizadas em uma região do pâncreas conhecida como Ilhotas de Langerhans. Com a ausência da insulina, os níveis de glicemia no sangue não abaixam e não há ação para impedir a influência do glucagon.

O "padrão ouro" de tratamento da doença é por meio de injeções de insulina, desde a descoberta da doença, em 1922. Os pacientes precisam receber as doses da substância durante boa parte da vida. No universo de todas as formas de diabetes, o tipo 1 responde por 10% dos casos e a maior parte das pessoas com o desenvolve antes dos 30 anos.

Meditação altera estrutura do cérebro em oito semanas

Este estudo reforça resultados de pesquisas anteriores ao eliminar outros efeitos e documentar que as diferenças foram efetivamente produzidas pela meditação.

Massa cinzenta

Dois meses de prática de meditação são suficientes para gerar mudanças mensuráveis nas regiões do cérebro associadas à memória, ao sentido de si mesmo, à empatia e ao estresse.

Em um estudo que será publicado na revista Psychiatry Research, uma equipe liderada por cientistas do Hospital Geral de Massachusetts (MGH) relata os resultados deste que é o primeiro estudo a documentar alterações na massa cinzenta do cérebro produzidas pela meditação.

Os praticantes de meditação sempre afirmaram que, além da sensação de relaxamento e tranquilidade física, eles experimentam benefícios cognitivos e psicológicos de longa duração.

Os cientistas agora confirmaram essas alegações e demonstraram que elas estão associadas a alterações físicas reais no cérebro.

Meditação que altera o cérebro

Estudos anteriores de vários grupos encontraram diferenças estruturais entre os cérebros de praticantes de meditação experientes e de indivíduos sem história de meditação, sendo observado um espessamento do córtex cerebral em áreas associadas com a atenção e a integração emocional.

Este estudo reforça essas conclusões ao eliminar outros efeitos e documentar que tais diferenças foram efetivamente produzidas pela meditação.

O estudo usou imagens de ressonância magnética do cérebro dos participantes.

Os participantes relataram também redução do nível de estresse, que foram correlacionados com a diminuição da densidade da massa cinzenta na amígdala, que é conhecida por desempenhar um papel importante na ansiedade e no estresse, mas também na sociabilidade.

Plasticidade do cérebro

Por muito tempo os cientistas acreditaram ter "evidências" de que o cérebro era uma estrutura fixa, com um número de neurônios que só fazer decrescer ao longo da vida.

Hoje já é reconhecido não apenas que o cérebro é dotado de uma incrível plasticidade, mas também que mudanças no cérebro podem ser induzidas voluntariamente.

"É fascinante ver a plasticidade do cérebro e que, praticando a meditação, podemos desempenhar um papel ativo para mudar nosso cérebro e aumentar o nosso bem-estar e nossa qualidade de vida," diz Britta Hölzel, da Universidade de Giessen, na Alemanha, coautora do estudo.

Molécula assassina pode se tornar protetora das células

Descobrindo como a chamada molécula assassina atua no processo de morte programada das células, cientistas querem transformá-la em molécula salvadora das células afetadas por doenças degenerativas.

Apoptose

Um estudo internacional publicado na primeira edição de 2011 da revista científica Molecular Cell descreve o mecanismo pelo qual a molécula ARTS, conhecida como "molécula assassina", regula o processo de morte celular.

A ARTS é uma proteína localizada na mitocôndria que está relacionada com a apoptose, evento que acarreta a morte celular programada.

O artigo, que tem entre seus autores um brasileiro, pode ajudar a explicar por que muitos tumores malignos são difíceis de reduzir.

"Sabe-se que a ARTS interage com outra molécula, a XIAP, mas o mecanismo de como isso ocorre e o apelo farmacológico que isso pode trazer foram o que levaram nossa pesquisa ser aceita pela revista", disse Ricardo Corrêa, pesquisador sênior do Sanford-Burnham Medical Research Institute, nos Estados Unidos.

Morte programada

Muitas células, velhas ou doentes, do corpo humano passam pela morte celular programada, um processo peculiar de eliminação que é também considerado importante na modulação da progressão do câncer.

Nesse processo, a ARTS é ligada à XIAP, responsável por regular a ação de caspases (enzimas inibidoras da apoptose) por meio do fluido intracelular. A morte da célula ocorre quando a ARTS é liberada.

Tal atividade, até então pouco conhecida, necessita de um estímulo para ocorrer. O trabalho de Corrêa e colegas desvenda como a proteína XIAP é sequestrada e inibida pela ARTS.

No estudo, o grupo descreve o papel de uma terceira proteína, Siah, na atividade pró-apoptótica da proteína ARTS liberada. Nesse processo, o novo componente participa por meio da ubiquitinação, processo em que as células indesejadas são marcadas com uma proteína chamada ubiquitina para que possam ser degradadas pelas organelas proteossomas.

A ARTS atua como um sinalizador para atrair o ataque de Siah à XIAP e essa atividade ocasiona a morte da célula. Em alguns casos de câncer infantil, como leucemia linfoblástica aguda ou leucemia melogênica aguda, há uma perda superior a 70% da proteína encontrada na mitocôndria, o que evidencia o papel de ARTS como inibidor do processo de oncogênese.

Vida programada

Corrêa destaca também o efeito contrário à morte celular que a mesma proteína pode vir a ter. "O próximo passo da pesquisa é o desenvolvimento de terapias citoprotetoras e peptídeos que tenham funções análogas à ARTS", disse.

"O efeito contrário, no qual temos a elevação de XIAP, também é interessante. Não do ponto de vista oncológico, mas, por exemplo, na preservação de neurônios", indicou.

Nesse caso, o grupo pretende desenvolver peptídeos capazes de sequestrar a proteína Siah do processo para que seja possível inibir a apoptose, criando, com isso, um efeito protetor da célula.

A ideia é obter peptídeos em porções similares à ARTS para que possam corromper as ligações das moléculas de Siah. Com isso, a atividade de XIAP é afetada, o que pode evitar a morte celular.

Benefícios

Doenças do sistema nervoso responsáveis pela degradação das células neurais, como Parkinson, Huntington, Alzheimer e esclerose múltipla podem ser beneficiadas com o estudo. Outro dado importante para o desenvolvimento de drogas, tanto para o câncer como para doenças do sistema nervoso, é a localização da molécula.

"De acordo com a região onde a ARTS está ligada a XIAP, podemos desenvolver peptídeos com ações miméticas de ARTS e modular eventos de aumento ou diminuição de XIAP, enfocando um papel oncológico ou de proteção neuronal", disse Corrêa.

Anestesia local altera autopercepção

Ilusões durante anestesia

Muitos pacientes relatam "ilusões" quando se submetem a algum procedimento sob a ação de anestesia local.

O Dr. Stein Silva e seus colegas do Instituto Nacional de Pesquisas Médicas (Inserm) da França resolveram estudar esses fenômenos.

Os pesquisadores demonstraram que o fato de anestesiar um único braço altera a atividade cerebral, afetando rapidamente a percepção corporal do indivíduo.

Os resultados foram divulgados no último exemplar da revista Anesthesiology.

Anestesia como terapia

Pesquisas recentes em neurociências têm mostrado que o cérebro é uma estrutura dinâmica - por muito tempo os cientistas acreditaram que o cérebro tinha uma quantidade fixa de neurônios, cuja morte explicaria o declínio cognitivo na velhice.

Hoje já sabe que esta teoria não é válida. Fenômenos como a aprendizagem, a memorização, ou a recuperação de um AVC, são possibilitadas pelas propriedades plásticas do cérebro, que se ajusta às necessidades.

O objetivo final do trabalho é tentar entender como os circuitos neuronais são reorganizados no exato momento em que a anestesia faz efeito, e aproveitar a própria anestesia para "reconfigurar" corretamente esses circuitos após o trauma, ou seja, após a percepção da ilusão.

Os resultados vão permitir que, no futuro, as técnicas anestésicas possam ser usadas para tratar, por exemplo, a dor descrita pelos pacientes amputados, no que é conhecido como "membro fantasma".

Ilusão do membro fantasma

Infelizmente, a plasticidade cerebral não tem sempre um efeito benéfico.

Por exemplo, alguns pacientes amputados portadores de dor crônica(conhecida como dor do membro fantasma) sentem como se seu membro faltante "ainda estivesse lá".

• Massagem virtual alivia dores em membros amputados

Essas ilusões do membro fantasma estão relacionadas com o surgimento no cérebro de representações incorretas da parte do corpo que foi perdida.

E pessoas sob anestesia local relatam ter experimentado essas mesmas imagens falsas.

Com base nessas observações, os pesquisadores queriam descobrir se a anestesia pode, além de cumprir sua função principal, induzir fenômenos comparáveis no cérebro, o que abre caminho para que os anestésicos sejam utilizados como ferramenta terapêutica capaz de modular a atividade do cérebro.

Fenômenos durante a anestesia

Os pesquisadores observaram três fenômenos com base nos testes em pacientes com um braço anestesiado:

1. Todos os pacientes descreveram falsas sensações em seu braço (inchaço, diferença no tamanho e na forma, posturas imaginárias);
2. em geral, os pacientes sob anestesia demoraram mais tempo para distinguir entre a mão esquerda e a mão direita e fizeram a indicação errada muito mais do que as pessoas que não se encontravam sob anestesia;
3. os melhores resultados foram obtidos quando o membro anestesiado estava visível para o paciente.

Em outras palavras, anestesiar a mão modifica a atividade cerebral e rapidamente muda a maneira como percebemos o mundo exterior e o nosso próprio corpo.

A equipe agora irá usar ressonância magnética funcional para caracterizar as regiões afetadas no cérebro.

Eles também esperam que seja possível utilizar a anestesia para fins terapêuticos no futuro modulando a plasticidade pós-lesional - a dor crônica em pacientes amputados e uma melhor recuperação das pessoas que sofrem lesões cerebrais.

Membrane Molecule Keeps Nerve Impulses Hopping

ScienceDaily (Jan. 26, 2011) — New research from the University of North Carolina at Chapel Hill School of Medicine describes a key molecular mechanism in nerve fibers that ensures the rapid conductance of nervous system impulses.

Mouse sciatic nerve myelinated axons immunostained against three proteins: Neurofascin 186 at the node of Ranvier (green), Contactin-associated protein at the paranodes (blue) and potassium channels at the juxtaparanodes (red).

The findings appear online Jan. 27, 2011 in the journal Neuron.

Our hard-wired nerve fibers or axons rely on an insulating membrane sheath, the myelin, made up of fatty white matter to accelerate the rate of transmission of electrical impulses from the brain to other parts of the body.

Myelin thus acts to prevent electrical current from leaking or prematurely leaving the axon. However, the myelin surrounding the axon isn't continuous; there are regularly spaced unmyelinated gaps about 1 micrometer wide along the axon. These unmyelinated regions named as nodes of Ranvier are where electrical impulses hop from one node to the next along the axon, at rates as fast as 160 meters per second (360 mph).

Determining exactly how the nodes of Ranvier function and how they are assembled, has fired the interest of neuroscientists for more than a century," said UNC neuroscientist Manzoor Bhat, PhD, Professor of Cell and Molecular Physiology in the UNC Neuroscience Research Center. "The answers may also provide important clues to the development of targeted treatments for multiple sclerosis and other disorders involving demyelination and/or disorganization of nodes of Ranvier."

Bhat and colleagues focused on a protein called Neurofascin 186, which accumulates in the membranes of axons at the nodes of Ranvier. Together with proteins Ankyrin-G and sodium channels, these molecules form a complex that facilitates passage of sodium ions through the channels in axons, thus making them paramount for the propagation of nerve impulses along myelinated nerve fibers.

Bhat's team had previously identified a homolog of Neurofascin in laboratory studies of Drosophila nerve fibers, and because its in vivo function had not been clearly defined in a mammalian system, they decided to study the function of this protein in laboratory mice.

Using targeted gene deletion methods, the UNC scientists genetically engineered mice lacking Neurofascin 186 in their neurons. "This caused the failure of sodium channels and Ankyrin-G to accumulate at the nodes of Ranvier. The result was paralysis, as there was no nerve impulse conductance," Bhat said.

According to Bhat, Neurofascin is an adhesion molecule that serves as the nodal organizer. "Its job is to cluster at the nodes of Ranvier. In doing so, it brings together sodium channels and Ankyrin-G where they interact to form the nodal complex. And if you don't have this protein, the node is compromised and there is no impulse propagation along the axon."

In further analysis, the researchers identified another important function of the nodes of Ranvier in myelinated nerve cells: to act as barriers to prevent the invasion of the nodal gap by neighboring paranodal molecular complexes. "So this tells us that sodium channels, Neurofascin 186, and Ankyrin-G must always remain in the node to have functional organization. If they don't, the flanking paranodes will move in and occupy the nodal gap and block nerve conduction," Bhat said.

The UNC neuroscientists see clinical implications for human disease. "In MS, for example, the proteins that make up the nodal complex start diffusing out from their normal location once you start losing the myelin sheath. If we can restore the nodal complex in nerve fibers, we may be able to restore some nerve conduction and function in affected axons." Their future studies are aimed at understanding whether the nodal complex could be reorganized and nerve conduction restored in genetically modified mutant mice.

"The discovery of an essential gap protein is exciting because it opens up the possibility that tweaking the protein could restore normal gap function in people with multiple sclerosis and other diseases in which the myelin sheaths and gaps deteriorate over time," said Laurie Tompkins, PhD, who oversees Manzoor Bhat's and other neurogenetics grants at the National Institutes of Health.

Support for the research came from the National Institute of General Medical Sciences, the National Institute of Neurological Disorders & Stroke of the National Institutes of Health and the National Multiple Sclerosis Society.

UNC co-authors are postdoctoral fellow Courtney Thaxton, PhD; research specialist, Anilkumar Pillai; and graduate student, Alaine Pribisco. Dr. Jeffrey Dupree, assistant professor at Virginia Commonwealth University, collaborated in these studies.

Chemists Document Workings of Key Staph Enzyme -- And How to Block It

ScienceDaily (Jan. 26, 2011) — Researchers have determined the structure and mechanism of an enzyme that performs the crucial first step in the formation of cholesterol and a key virulence factor in staph bacteria.

Chemists led by Illinois professor Eric Oldfield, center, determined the structure of a key enzyme that could lead to more efficient drugs to treat staph infections, parasites and high cholesterol. The research team, from left, research scientist Yonghui Zhang, graduate student Fu-Yang Lin, research scientist Rong Cao and postdoctoral associate Ke Wang.

Chemists at the University of Illinois and collaborators in Taiwan studied a type of enzyme found in humans, plants, fungi, parasites, and many bacteria that begins the synthesis of triterpenes -- one of the most abundant and most ancient classes of molecules. Triterpenes are precursors to steroids such as cholesterol.

"These enzymes are important drug targets," said chemistry professor Eric Oldfield, who co-led the study. "Blocking their activity can lead to new cholesterol-lowering drugs, antibiotics that cure staph infections, and drugs that target the parasites that cause tropical maladies such as Chagas disease -- a leading cause of sudden death in Latin America."

For the study, the team picked a representative enzyme, dehydrosqualene synthase (CrtM), from the Staphylococcus aureus bacterium. Staph is one of the most common, yet notoriously hard to kill, bacterial infections. A key reason for staph's resilience is a golden-colored coating called staphyloxanthin that protects it from the body's immune system. CrtM catalyzes the first reaction in making staphyloxanthin, so inhibiting it would strip the bacteria of their protective coats and leave them vulnerable to attack by white blood cells.

The researchers already knew what CrtM looked like and its end product, but they didn't know how the enzyme did its job. Uncovering the mechanism of action would enable scientists to design better inhibitors, and even tailor them to other targets.

The team crystallized the enzyme and soaked it with intermediates and inhibitors. They then studied the complex structures by X-ray crystallography using the synchrotron at the Advanced Photon Source at Argonne National Laboratory.

They found that CrtM performs a two-step reaction, individually removing two diphosphate groups from the substrate. The substrate switches between two active sites within the enzyme as the reaction progresses. The most effective inhibitors bind to both sites, blocking the enzyme from any action.

"The leads that people have been developing for treating these diseases really haven't had any structural basis," said Oldfield, also a professor of biophysics. "But now that we can see how the protein works, we're in a much better position to design molecules that will be much more effective against staph infections and parasitic diseases, and potentially, in cholesterol-lowering."

The researchers' inhibitor technologies have been licensed to AuricX Pharmaceuticals, which recently received a grant from the Texas Emerging Technology Fund for preclinical testing in staph infections.

The team published its work in the Proceedings of the National Academy of Sciences. The work was sponsored by the National Institutes of Health and the National Science Council. Co-authors were U. of I. graduate students Fu-Yang Lin and Yi-Liang Liu, research scientists Rong Cao and Yonghui Zhang, and postdoctoral associate Ke Wang. Taiwan collaborators included Chia-I Liu, Wen-Yih Jeng, Tzu-Ping Ko and Andrew H. Wang.

New Map of Brain Connectivity Shows Changes During Development

ScienceDaily (Jan. 26, 2011) — Connected highways of nerve cells carry information to and from different areas of the brain and the rest of the nervous system. Scientists are trying to draw a complete atlas of these connections -- sometimes referred to as the "connectome" -- to gain a better understanding of how the brain functions in health and disease.

New research conducted at The Scripps Research Institute shows that this road atlas undergoes constant revisions as the brain of a young animal develops, with new routes forming and others dropping away in a matter of hours. "We have shown that the connectome is dynamic during development, but we expect it will also change according to an individual's experience and in response to disease," says Scripps Research Professor Hollis Cline, senior author of the study.

The study, published in the January 27, 2011 issue of Neuron, dispels some long-held notions of how connections between nerve cells are established, highlighting the interplay between formation and removal. The findings have implications for conditions in which these mechanisms may have gone awry, such as autism, schizophrenia, and perhaps Alzheimer's.

A Dynamic Map

Cline's group has been studying how experience -- the different sights and sounds and other environmental cues picked up by neurons -- change connections and activities in the brain through a process known as plasticity. "Based on our prior research we expected that the connectome would be dynamic," says Cline.

To start to document how the connectome changes and test current models of how the map is laid out, Cline and colleagues turned to the frog Xenopus laevis. They combined two new techniques to map in great detail all the connections that form during tadpole development in an area of the brain that receives and interprets signals from the eyes.

In the nervous system, information is handed from one nerve cell to another through two arms, called dendrites and axons, stretching out from opposite sides of each cell. The axon carries information away from a nerve cell, or neuron, and passes it to the dendrite of another; dendrites receive the information, which travels through the cell to the axon. The region where information is transferred from one neuron to another (and where axons and dendrites connect) is called the synapse.

The Cline group's approach relied on taking time-lapse images of growing axons and dendrites over several days. The researchers then zoomed in on synapses that formed using electron microscopy, a technique that magnifies objects up to 2 million times. This close-up view revealed some "surprising results about synapse formation and plasticity," says Cline.

Promiscuous Partners

Models of synapse formation typically show that as dendrites extend new branches, each branch forms an immature synapse with a target axon that is later either maintained or eliminated. But Cline's study shows instead the process is not as selective. Each growing dendrite samples not one but many possible partners before selecting one with which to maintain contact.

As new branches grow from dendrites, they form many immature synapses on axons. Then, as each new dendrite branch matures, most immature synapses are eliminated; the ones not eliminated mature into stable synapses. "We did not know that dendrites make so many connections that are then removed," says Cline. "It is always fun in science when you see that what was expected is not what actually happens."

Cline and colleagues also discovered that axon synapses don't form, as previously thought, on growing branches but rather at swellings, called boutons, located on stable axon branches.

Another surprise was that when growing dendrites go searching for potential partners, they reach out to axon boutons that had previously connected with other dendrites -- "as if they were attracted to a restaurant that already has a line at the door, rather than trying a brand new one," says Cline.

Over time, these boutons decrease the number of connected partners to form mature connections with single dendrites.

Shining the Spotlight on Elimination

Up until now, researchers had focused their work primarily on determining how new connections form and on finding ways to enhance such formation. But Cline's findings that so many immature connections are removed during development puts greater emphasis on the process of elimination, she says.

Several studies have shown that brain activity helps new connections to form. Thus, Cline asked whether activity is also required for synapse elimination to occur. To answer this question, Cline and colleagues shut off activity in the visual system by keeping some of the tadpoles in darkness. These animals had many more immature synapses than animals that could see, indicating brain activity is needed for selecting which synapses should be eliminated.

The team now plans to look in more detail at the molecular signals involved in the elimination process, hoping to identify any genes that might be responsible. "It is possible that some genetic diseases are caused by the inefficient elimination of synapses," explains Cline. For example, individuals with a disease known as fragile X, a leading cause of mental retardation, are thought to have too many synapses, suggesting elimination did not occur properly.

Potential 'Cure' for Type 1 Diabetes

ScienceDaily (Jan. 26, 2011) — Type 1 diabetes could be converted to an asymptomatic, non-insulin-dependent disorder by eliminating the actions of a specific hormone, new findings by UT Southwestern Medical Center researchers suggest.

These findings in mice show that insulin becomes completely superfluous and its absence does not cause diabetes or any other abnormality when the actions of glucagon are suppressed. Glucagon, a hormone produced by the pancreas, prevents low blood sugar levels in healthy individuals. It causes high blood sugar in people with type 1 diabetes.

"We've all been brought up to think insulin is the all-powerful hormone without which life is impossible, but that isn't the case," said Dr. Roger Unger, professor of internal medicine and senior author of the study appearing online and in the February issue of Diabetes. "If diabetes is defined as restoration of glucose homeostasis to normal, then this treatment can perhaps be considered very close to a 'cure.' "

Insulin treatment has been the gold standard for type 1 diabetes (insulin-dependent diabetes) in humans since its discovery in 1922. But even optimal regulation of type 1 diabetes with insulin alone cannot restore normal glucose tolerance. These new findings demonstrate that the elimination of glucagon action restores glucose tolerance to normal.

Normally, glucagon is released when the glucose, or sugar, level in the blood is low. In insulin deficiency, however, glucagon levels are inappropriately high and cause the liver to release excessive amounts of glucose into the bloodstream. This action is opposed by insulin, which directs the body's cells to remove sugar from the bloodstream.

Dr. Unger's laboratory research previously found that insulin's benefit resulted from its suppression of glucagon.

In type 1 diabetes, which affects about 1 million people in the U.S., the pancreatic islet cells that produce insulin are destroyed. As a countermeasure to this destruction, type 1 diabetics currently must take insulin multiple times a day to metabolize blood sugar, regulate blood-sugar levels and prevent diabetic coma. They also must adhere to strict dietary restrictions.

In this study, UT Southwestern scientists tested how mice genetically altered to lack working glucagon receptors responded to an oral glucose tolerance test. The test -- which can be used to diagnose diabetes, gestational diabetes and prediabetes -- measures the body's ability to metabolize, or clear, glucose from the bloodstream.

The researchers found that the mice with normal insulin production but without functioning glucagon receptors responded normally to the test. The mice also responded normally when their insulin-producing beta cells were destroyed. The mice had no insulin or glucagon action, but they did not develop diabetes.

"These findings suggest that if there is no glucagon, it doesn't matter if you don't have insulin," said Dr. Unger, who is also a physician at the Dallas VA Medical Center. "This does not mean insulin is unimportant. It is essential for normal growth and development from neonatal to adulthood. But in adulthood, at least with respect to glucose metabolism, the role of insulin is to control glucagon.

"And if you don't have glucagon, then you don't need insulin."

Dr. Young Lee, assistant professor of internal medicine at UT Southwestern and lead author of the study, said the next step is to determine the mechanism behind this result.

"Hopefully, these findings will someday help those with type 1 diabetes," Dr. Lee said. "If we can find a way to block the actions of glucagon in humans, then maybe we can minimize the need for insulin therapy."

Dr. Unger said anything that reduces the need for injected insulin is a positive.

"Matching the high insulin levels needed to reach glucagon cells with insulin injections is possible only with amounts that are excessive for other tissues," he said. "Peripherally injected insulin cannot accurately duplicate the normal process by which the body produces and distributes insulin. If these latest findings were to work in humans, injected insulin would no longer be necessary for people with type 1 diabetes."

Dr. May-Yun Wang, assistant professor of internal medicine at UT Southwestern, and researchers from the Albert Einstein College of Medicine also contributed to the work.

The study was supported in part by the VA North Texas Health Care System, the American Diabetes Association and the National Institutes of Health.

Discovery of a Biochemical Basis for Broccoli's Cancer-Fighting Ability

ScienceDaily (Jan. 26, 2011) — Scientists are reporting discovery of a potential biochemical basis for the apparent cancer-fighting ability of broccoli and its veggie cousins. They found for the first time that certain substances in the vegetables appear to target and block a defective gene associated with cancer.

Broccoli. Scientists are reporting discovery of a potential biochemical basis for the apparent cancer-fighting ability of broccoli and its veggie cousins. They found for the first time that certain substances in the vegetables appear to target and block a defective gene associated with cancer.

Their report, which could lead to new strategies for preventing and treating cancer, appears in ACS' Journal of Medicinal Chemistry.

Fung-Lung Chung and colleagues showed in previous experiments that substances called isothiocyanates (or ITCs) -- found in broccoli, cauliflower, watercress, and other cruciferous vegetables -- appear to stop the growth of cancer. But nobody knew exactly how these substances work, a key to developing improved strategies for fighting cancer in humans. The tumor suppressor gene p53 appears to play a key role in keeping cells healthy and preventing them from starting the abnormal growth that is a hallmark of cancer. When mutated, p53 does not offer that protection, and those mutations occur in half of all human cancers. ITCs might work by targeting this gene, the report suggests.

The scientists studied the effects of certain naturally-occurring ITCs on a variety of cancer cells, including lung, breast and colon cancer, with and without the defective tumor suppressor gene. They found that ITCs are capable of removing the defective p53 protein but apparently leave the normal one alone. Drugs based on natural or custom-engineered ITCs could improve the effectiveness of current cancer treatments or lead to new strategies for treating and preventing cancer.

The authors acknowledged funding from the Ruth L. Kirschstein National Research Service Award and a grant from the National Cancer Institute of the National Institutes of Health.

Food-Borne Bacteria Causes Potentially Fatal Heart Infection

ScienceDaily (Jan. 26, 2011) — Researchers at the University of Illinois at Chicago College of Medicine have found that particular strains of a food-borne bacteria are able to invade the heart, leading to serious and difficult-to-treat heart infections.

Listeria monocytogenes cardiac-invasive strain replicating and moving within infected heart cells. The bacteria (red rods) invade heart cells, multiply, and begin to move through the cell by rearranging cell structural proteins (green) that initially coat the bacteria (green and red rods) and then form long comet tails located directly behind moving bacteria.

The study is available online in theJournal of Medical Microbiology.

The bacteria Listeria monocytogenesis commonly found in soft cheeses and chilled ready-to-eat products. For healthy individuals, listeria infections are usually mild, but for susceptible individuals and the elderly, infection can result in serious illness, usually associated with the central nervous system, the placenta and the developing fetus.

About 10 percent of serious listeria infections involve a cardiac infection, according to Nancy Freitag, associate professor of microbiology and immunology and principle investigator on the study. These infections are difficult to treat, with more than one-third proving fatal, but have not been widely studied and are poorly understood.

Freitag and her colleagues obtained a strain of listeria that had been isolated from a patient with endocarditis, or infection of the heart.

"This looked to be an unusual strain, and the infection itself was unusual," she said. Usually with endocarditis there is bacterial growth on heart valves, but in this case the infection had invaded the cardiac muscle.

The researchers were interested in determining whether patient predisposition led to heart infection or whether something different about the strain caused it to target the heart.

They found that when they infected mice with either the cardiac isolate or a lab strain, they found 10 times as much bacteria in the hearts of mice infected with the cardiac strain. In the spleen and liver, organs that are commonly targeted by listeria, the levels of bacteria were equal in both groups of mice.

Further, the researchers found that while the lab-strain-infected group often had no heart infection at all, 90 percent of the mice infected with the cardiac strain had heart infections. The researchers obtained more strains of listeria, for a total of 10, and did the same experiment. They found that only one other strain also seemed to also target the heart.

"They infected the heart of more animals and were always infecting heart muscle and always in greater number," Freitag said. "Some strains seem to have this enhanced ability to target the heart for infection."

Freitag's team used molecular genetics and cardiac cell cultures to explore what was different about these two strains.

"These strains seem to have a better ability to invade cardiac cells," she said. The results suggest that these cardiac-associated strains display modified proteins on their surface that enable the bacteria to more easily enter cardiac cells, targeting the heart and leading to bacterial infection.

"Listeria is actually pretty common in foods," said Freitag. "And because it can grow at refrigerated temperatures, as foods are being produced with a longer and longer shelf life, listeria infection may become more common. In combination with an aging population that is more susceptible to serious infection, it's important that we learn all we can about these deadly infections."

The study was supported by a Public Health Service Grant; by Public Health Service post-doctoral training fellowships; and an American Heart Association Predoctoral Fellowship.