Saving Lives: CVM researchers' efforts aim to assist both animals and humans

Friday, January 19, 2024

Media Contact: Taylor Bacon | Public Relations and Marketing Coordinator | 405-744-6728 | taylor.bacon@okstate.edu

The research at the Oklahoma State University College of Veterinary Medicine covers the expanse of One Health, from the bench to the clinic.

OSU’s We Are Land-Grant strategy has One Health as a pillar of the institution’s mission, aiming to use animal medical research to aid humans. CVM researchers are constantly looking to aid in that connection, as well as continue their work in serving the state by advancing animal health.

Diabetic Difficulties

Diabetes and obesity are concerns in both human and veterinary medicine across the globe.

Dr. Veronique Lacombe, professor of physiological sciences and director of the CVM’s Comparative Metabolism Research Laboratory, said approximately 80 million dogs and cats in the U.S. are at increased risk for weight-related disorders such as diabetes, hypertension and cancer.

In humans, diabetes afflicts 37.3 million Americans and 537 million people worldwide. The condition is characterized by high blood sugar levels over prolonged time periods and can lead to severe complications if not effectively managed.

OSU researchers are hoping to better understand the different types of diabetes and ways to treat them.

In type 1 diabetes, the body’s immune system attacks and destroys insulin-producing cells. Comparatively, type 2 diabetes is characterized by insulin resistance and impaired insulin secretion.

Insulin is produced by the pancreas, which is part of the endocrine system and for Dr. Henrique Cheng, associate professor of physiological sciences, that area of study has always been of interest to him.

“From my veterinary school days and throughout my professional career, I was always intrigued by how hormones influence various organs to regulate bodily functions,” Cheng said. “My graduate training further piqued my interest in diabetes, especially given its prevalence in our family.”

Cheng’s laboratory is focused on two areas of diabetes. One is identifying hormones and natural compounds that target the pancreas and prompt insulin secretion to reduce blood sugar levels in type 2 adult diabetic patients.

“In this type of diabetes, there are often problems associated with insulin secretion from pancreatic cells,” Cheng said. “We further characterize the molecular mechanism of action of these hormones and compounds, which is essential for drug development to treat the disease.”

This research has identified several hormones and natural compounds from fruits and vegetables that can stimulate insulin secretion from pancreatic cells. Many of these hormones are more commonly known for their effect in other organs where they control processes such as reproduction or bone formation.

The other area Cheng’s lab is focused on is attempting to regenerate functional insulin producing cells using gene therapy and stems cells for the treatment of type 1 juvenile diabetes.

“In this case, there is destruction of insulin cells by the immune system,” Cheng said. “Therefore, one aspect that needs addressed is restoration of the cell population. In our studies, we utilize pancreatic cell lines, primary cells, pancreatic islets and diabetic animal models.

“We have demonstrated an animal model of type 1 diabetes can be reversed by attracting transplanted bone marrow stem cells to the diseased pancreas with homing factors.”

Results showed all animals had lower blood glucose after treatment and responded to glucose tolerance tests in a similar manner as that of the control non-diabetic animals.

As Cheng’s lab continues to make progress in the field of diabetes research, he is excited about the potential discoveries that lie ahead. The lab is exploring non-invasive treatment options to reduce the need for injections and frequent blood tests, making the daily lives of diabetic patients more comfortable and stress free.

“Although we are not there yet, the discovery of new hormones and compounds and methods to induce insulin regeneration are bringing us closer to a cure for diabetes,” Cheng said.

Cheng’s team isn’t the only CVM laboratory working to improve the lives of those with diabetes. Lacombe focuses on investigating glucose metabolism during diabetes and obesity.

“Given the global epidemic of these metabolic diseases that significantly contribute to the risk of cardiovascular and pulmonary diseases, our work aims to unravel the underlying pathogenic processes associated with these conditions,” Lacombe said. 

In Lacombe’s lab, researchers have demonstrated that enhanced calcium metabolism in the heart not only improved cardiac glucose metabolism but also partially mitigated diabetes. They found the heart secretes proteins which can regulate whole-body glucose= homeostasis and effectively aid in managing hyperglycemia by enhancing glucose transport in diabetic patients’ tissue.

“Understanding that the heart secretes proteins capable of regulating glucose levels opens new avenues to treat diabetes and its complications, such as cardiovascular diseases,” Lacombe said.

Lacombe said her team is committed to developing novel metabolic therapeutic strategies for diabetic patients who are also facing respiratory illnesses.

Additionally, researchers in the laboratory are exploring the development of an intranasal drug that could be administered one to two times per week to regulate diabetic patients’ blood sugar levels.

“We are optimistic that the continued efforts of the Comparative Metabolism Research Laboratory will yield significant advancements in the field, ultimately leading to improved health outcomes and a better quality of life for individuals affected by these complex health challenges,” Lacombe said.

Fixing Foals

Not all of OSU’s research takes place in a lab, as the CVM uses hands-on techniques with direct implications on the animal health industry.

In the clinic, Dr. Mike Schoonover, professor of veterinary clinical sciences and equine surgery and sports medicine service chief, is evaluating the efficiency and safety of administering the antibiotic amikacin intravenously and by regional limb perfusion in neonatal foals. Schoonover was one of only three researchers on OSU’s campus to receive the 2023 OSU President’s Fellows Faculty Research Award for this project. 

Septicemia, a bacterial infection in the blood stream, is common in newborn foals and can result in life-threatening infections throughout the body. The joints and growth plates are common secondary sites of infection and can have severe long-term effects on the foal’s soundness.

“Infection in one or more of a foal’s joint can cause permanent damage that could lead to chronic lameness and developmental orthopedic disorders,” Schoonover said.

Once infection in a joint is diagnosed, aggressive treatment is the only way to maximize the chance of success. However, even persistent treatment is often not enough to prevent irreversible damage within the foal’s joints. Reported survival rates for these foals range from just 42% to 89%.

Antimicrobials are often used in the treatment of bacterial infections, but when given systemically at the recommended dosages, they often don’t reach the joints at a high enough concentration to eliminate infection. Increasing the total dosage can also lead to negative side effects such as kidney failure. This leaves veterinarians in a dilemma as to how they adjust the systemic dose to account for a dose administered locally.

“A few years ago, we had a very sick foal present to the hospital in need of both systemic and intra-articular antibiotics,” Schoonover said. “It had infection in multiple joints and antibiotics were given both intravenously and intra-articular. We questioned the safety and efficacy of the antibiotic dosage because there were no scientific studies published to help guide our dosing protocol.”

This led him and his team to explore alternative foal treatment options. The team conducted a study in 2018 evaluating antibiotic delivery by intravenous and intra-articular routes. Schoonover presented these results to the veterinary profession at the annual meeting of the American Association of Equine Practitioners in Denver in 2019.

“Intravenous regional limb perfusion, or IVRLP, is a technique of local antimicrobial administration where a tourniquet is utilized to temporarily isolate the blood circulation of a limb while a relatively low dose of antimicrobial is injected directly into a vein of the limb,” Schoonover said. “Once administered, the antimicrobial remains in the limb, achieving a very\ high concentration until the tourniquet is removed, usually in 20 to 30 minutes, allowing normal blood circulation to resume.”

IVRLP is a well-utilized technique in adult horses, but little to no previous research existed on the efficacy and safety of IVRLP in neonatal foals.

Amikacin is one of many different antibiotics used to treat infection in foals and is known for its success against common orthopedic pathogens. In this study, researchers administered two IVRLP amikacin treatment protocols to eight foals and measured the blood and joint fluid concentrations of amikacin for each protocol over a 24-hour period. Data from this study are currently being analyzed and the results and conclusions will be available soon.

“The goal of the study is to provide needed scientific evidence of the effectiveness and safety of concurrent intravenous and IVRLP with amikacin for the treatment and infection of neonatal foal joints,” Schoonover said. “It will also help guide future IVRLP research in foals using different medications and techniques.”

The horse industry is vital to the state of Oklahoma and has a major impact on the state’s economy and many residents’ quality of life. Newborn foals within the state, nation and worldwide seek to benefit from improved treatment protocol.

This research is crucial to the horse industry and animal health.

“Clinical research allows us to apply our clinical knowledge and/or results of basic research to live animal patients to determine treatment efficacy and safety, and report those results to the scientific community and practicing veterinarians,” Schoonover said. “Knowing how a treatment will affect a live animal patient is critically important in the practice of evidence-based medicine.”

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Photos By: Taylor Bacon and Kinsey Reed

Story By: Taylor Bacon | Vet Cetera Magazine