Breaking News
May 26, 2018 - Delivery of standardized diabetes care could help achieve equitable health outcomes for all patients
May 26, 2018 - FDA authorizes marketing of OsteoDetect software for detecting wrist fractures
May 26, 2018 - Children and adolescents growing up in extreme societal conditions more likely to resort to violence
May 26, 2018 - New study puts forth most comprehensive tree of life for malaria parasites
May 26, 2018 - New research shows why babies need to move in the womb
May 26, 2018 - UK steps forward to tackle global antimicrobial resistance
May 26, 2018 - CRISPR-Cas9-based strategy allows researchers to precisely alter hundreds of different genes
May 26, 2018 - UT Southwestern-led researchers find new way to determine prognosis of invasive kidney cancer
May 26, 2018 - Researchers develop film to prevent bacteria from growing on dental retainers and aligners
May 26, 2018 - Mobile health intervention for people with serious mental illness as effective as clinic-based treatment
May 26, 2018 - Vaginal estradiol tablets outperform moisturizers when treating vulvovaginal problems
May 26, 2018 - Researchers call for new genetic tests for congenital diseases
May 26, 2018 - KHN’s ‘What the Health?’ Campaign promises kept, plus ‘nerd reports’
May 26, 2018 - Lung-on-a-chip technology could streamline drug-testing for pulmonary fibrosis
May 26, 2018 - Study finds early antibiotic initiation for majority of premature infants
May 26, 2018 - New environmental monitoring project finds increased numbers of deer ticks in Southern Indiana
May 26, 2018 - Pediatricians Should Advocate for Life Support Training
May 26, 2018 - Cannabidiol significantly reduces seizures in patients with severe form of epilepsy
May 26, 2018 - Allergies can have serious, far-reaching consequences on adolescents
May 26, 2018 - Scientists develop lab-based system to study mechanisms of common liver disease
May 25, 2018 - New guidelines may help pathologists to more accurately classify and diagnose invasive melanoma
May 25, 2018 - Immune cells promote lung cancer metastases by forming clots in tumors, study finds
May 25, 2018 - Can Excess Weight in Toddlers Cause Brain Drain?
May 25, 2018 - Studying insight
May 25, 2018 - Researchers reveal potent new mechanism of action for treatment of IBD
May 25, 2018 - Study shows lack of follow-up care for patients with concussion
May 25, 2018 - Study establishes the importance of haploid cells
May 25, 2018 - Coveted BMJ award bestowed on The Clatterbridge Cancer Center
May 25, 2018 - AACN outlines evidence-based protocols and clinical strategies to manage alarms
May 25, 2018 - Origami inspires researchers to develop new solution for tissue regeneration
May 25, 2018 - Melorheostosis – Genetics Home Reference
May 25, 2018 - Non-addictive pain medication changing therapy for substance use disorders
May 25, 2018 - Delayed lactate measurements in sepsis patients increase risk of in-hospital death
May 25, 2018 - Researchers identify novel epigenetic mutations as cause of neurodevelopmental, congenital disorders
May 25, 2018 - UD researchers examine connection between DNA replication in HPV and cancer
May 25, 2018 - Researchers identify neurons that play key role in aggressive behavior
May 25, 2018 - Snail’s eye inspires new type of RIOCATH urinary catheter
May 25, 2018 - Russian researchers develop high-tech device-transformer for ultrasound examination
May 25, 2018 - Researchers discover unexpected chemosensor pathway for predator odor-evoked innate fear behaviors
May 25, 2018 - Researchers build 3-D printer that offers sweet solution to making detailed structures
May 25, 2018 - Nearly one in three people know someone addicted to opioids
May 25, 2018 - Research suggests link between faulty gene, alcohol, and heart failure
May 25, 2018 - New findings could help fine-tune treatment for cancer patients
May 25, 2018 - New cancer treatment approach targets specific sugar receptors
May 25, 2018 - Skin responsible for uptake of cancer-causing compounds during barbecuing than lungs
May 25, 2018 - Early-onset cannabis use linked to further drug abuse problems
May 25, 2018 - Covered California takes aim at hospital C-section rates
May 25, 2018 - FDA Approves Palynziq (pegvaliase-pqpz) for the Treatment of Adults with Phenylketonuria
May 25, 2018 - Arthritis Glossary
May 25, 2018 - Study links breast cancer to the body’s internal clock
May 25, 2018 - Strenuous exercise in teenage years may protect against height loss later in life
May 25, 2018 - FDA approves novel enzyme therapy for adults with rare and serious genetic disease
May 25, 2018 - New research project aims at developing effective interventions for kids with DLD
May 25, 2018 - Middlemen who save $$ on medicines — but maybe not for you
May 25, 2018 - Study sheds new light on sharp rise in fatal drug overdoses in recent years
May 25, 2018 - Students propose revision of listeriosis guidelines for safer pregnancy
May 25, 2018 - TNFi Exposure In Utero Does Not Up Serious Infection Risk
May 25, 2018 - Organization of cells in the inner ear enables the sense and sensitivity of hearing
May 25, 2018 - Yoga May Be Right Move Against Urinary Incontinence
May 25, 2018 - Drinking recommended amount of milk could protect obese children against metabolic syndrome
May 25, 2018 - New cytokine network can repair tissue damage in the intestine, study finds
May 25, 2018 - Lyme disease researcher dispels misconceptions about ticks and provides prevention tips
May 25, 2018 - Penn researchers find link between social media usage and underage drinking
May 25, 2018 - Unique nanotechnology method to simplify skin disease diagnosis
May 25, 2018 - Study reveals new protective mechanism for tumor cells in breast cancer
May 25, 2018 - FRAME Alternatives Laboratory chosen for major European liver research collaboration
May 25, 2018 - Study shows yogurt may dampen chronic inflammation linked to multiple diseases
May 25, 2018 - Invasive cancers that are born to be bad show detectable differences from harmless tumors
May 25, 2018 - Study identifies new mechanism involved in development of Lou Gehrig’s disease
May 25, 2018 - UAB professor receives award for malaria prevention study in pregnant women in Cameroon
May 25, 2018 - Study provides blueprint of how fruit flies can be used to screen potentially pathogenic human genes
May 25, 2018 - New drug-delivering nanoparticle could offer better way to treat brain tumors
May 25, 2018 - Kessler Foundation scientists compare two tests for assessing learning in individuals with MS
May 25, 2018 - Stroke Symptoms and Diagnosis (Beyond the Basics)
May 25, 2018 - Protein goes against the family to prevent cancer
May 25, 2018 - Drugmakers blamed for blocking generics have milked prices and cost U.S. billions
May 25, 2018 - Speakers announced for National Medicines Symposium 2018
May 25, 2018 - GSK Receives FDA Approval of Arnuity Ellipta for Asthma in Children From 5 Years of Age
May 25, 2018 - Pfizer settles kickback case related to copay assistance for $24m
May 25, 2018 - Nuclear pore functions are essential for T cell survival
Chemist finds how to control blood sugar without usual side effects

Chemist finds how to control blood sugar without usual side effects

image_pdfDownload PDFimage_print

Chemist Robert Doyle in the College of Arts and Sciences (A&S) at Syracuse University has figured out how to control glucose levels in the bloodstream without the usual side effects of nausea, vomiting or malaise.

Robert Doyle, the Laura J. and L. Douglas Meredith Professor of Teaching Excellence and professor of chemistry, is the inventor of a new compound that triggers the secretion of insulin in the pancreas without associated nausea. Working with colleagues at the University of Pennsylvania (Penn), the Seattle Children’s Hospital and SUNY Upstate Medical University, he has designed a conjugate of vitamin B12 that is bound to an FDA-approved drug known as Ex4.

Doyle’s compound, called B12-Ex4, expects to offer a broader scope of available treatment options for diabetes because of its ability to improve glucose tolerance without the associated side effects.

His findings are part of a groundbreaking paper he has co-authored in Diabetes, Obesity and Metabolism (John Wiley & Sons, 2018). A related paper of his addressing glucoregulation and appetite suppression is scheduled to run in Scientific Reports (Nature Publishing Group, 2018). “This represents an interesting new paradigm for the treatment of Type 2 diabetes, using so-called GLP1-R agonist drugs, which make up a multi-billion dollar industry,” says Doyle, also an associate professor of medicine at SUNY Upstate. “Our findings highlight the potential clinical utility of B12-Ex4 conjugates as therapeutics to treat Type 2 diabetes, with reduced incidence of adverse effects.”

Type 2 diabetes is marked by increased levels of glucose in the blood or urine, when the body is unable to use or produce enough insulin. Long-term complications include eye, kidney or nerve damage; heart attack or stroke; or problems with the wound-healing process.

Doyle’s discovery stems from his work with exenatide, a drug that causes the pancreas to secrete insulin when glucose levels are high. (Insulin is a hormone that moves glucose from the blood to various cells and tissues, where the sugar turns into energy.) Used to treat Type 2 diabetes, exenatide is part of a large class of medications called incretin mimetics. These injectable drugs bind to glucagon-like peptide receptors (GLP1-R) to stimulate the release of insulin.

A drawback of exenatide is that GLP1-R is found in the pancreas and brain. Stimulating the receptor in the pancreas leads to positive aspects of glucose control, but doing so in the hypothalamus (the part of the brain coordinating the nervous system and pituitary gland) causes malaise and nausea.

“We were able to mitigate the side effects of exenatide by preventing it from entering the brain, while allowing it to penetrate other areas of the body, such as the pancreas,” says Doyle, whose research focuses on the chemistry of B12, exploiting its properties and dietary pathway for drug delivery. “Our ability to ‘fix’ Ex-4 as a proof of concept could impact obesity and cancer treatment, since we can use our drug system to prevent or modulate central nervous system [CNS]-mediated side effects. In the case of Ex-4, this [side effect] was chronic nausea.”

Critical to Doyle’s research are GLP-1R agonists–synthetic, peptide-based chemicals that bind to organs or cells, causing them to produce a biological response. These peptide conjugates of insulin are the only known hormones able to decrease blood-sugar levels by enhancing the secretion of insulin. They do this by reducing food intake and body weight.

Doyle says these drugs are effective for treating obesity, but many Type 2 diabetics are not obese or overweight: “In fact, they should avoid losing weight altogether.”

Add to that the prevalence of nausea or vomiting, and the chances of skipping doses or discontinuing treatment increase considerably. “These adverse effects are surprisingly under-investigated, and they limit the full, widespread use and efficacy of GLP-1R agonists for the treatment of metabolic disease,” he continues.

In response to critical need, Doyle’s lab has spearheaded the development of a next-generation incretin therapeutic that controls blood sugar without causing a reduction in food intake or change in eating behavior. “This method of conjugation is ideal for the future treatment of Type 2 diabetes,” says Doyle, adding that Syracuse University owns the patent on this work. “It also may be broadly beneficial to other therapeutics that would benefit from reduced CNS penetrance.”

Doyle collaborated with Matthew Hayes, associate professor of neuroscience in the Department of Psychiatry in Penn’s Perelman School of Medicine, in the project’s experimental design and execution.

Since joining Syracuse’s faculty in 2005, Doyle has become a rising star in medicinal chemistry. His broad background in synthetic chemistry, drug delivery and protein biochemistry underscores his cross-cutting research, which has received support from multiple sources, including the National Institutes of Health, the American Chemical Society, the Serum Foundation and various industry partners.

Source:

Chemist Designs Diabetic Treatment Minus Harmful Side Effects

Tagged with:

About author

Related Articles