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New Therapy Could Reverse Type 1 Diabetes In Humans And Dogs

Discussion in 'Endocrinology' started by Dr.Scorpiowoman, Sep 12, 2018.

  1. Dr.Scorpiowoman

    Dr.Scorpiowoman Golden Member

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    Researchers at Purdue University and Indiana University School of Medicine (IU) are working with man’s best friend to cure one of his most insidious diseases.

    The scientists say a new therapy shows promise for long-term reversal of Type 1 diabetes in both humans and dogs.

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    Kelly Prinkey-Krupinski, 48, with her rescue dogs, Waffle, Splash and Gracie. Prinkey-Krupinski has been struggling with adult onset Type 1 diabetes for 12 years.

    Purdue reported this week that scientists achieved normal glucose levels in diabetes-induced mice by injecting them with a collagen solution mixed with pancreatic cells. It is the first minimally invasive therapy to successfully reverse Type 1 diabetes within 24 hours and maintain insulin independence for at least 90 days, scientists report.

    Researchers effectively ushered in healthy pancreatic cells like a Trojan horse, with the Trojan horse being a protein the body already makes for building muscles, bones, skin and blood vessels—collagen.

    According to Purdue University, the next step is a pilot clinical study in dogs with naturally occurring Type 1 diabetes, which will be conducted in collaboration with Purdue’s College of Veterinary Medicine.

    "We plan to account for differences from mouse to human by helping dogs first. This way, the dogs can inform us on how well the treatment might work in humans," said Clarissa Hernandez Stephens, first author on the research and a graduate researcher in Purdue’s Weldon School of Biomedical Engineering. Findings appear in early view for a forthcoming issue of the American Journal of Physiology – Endocrinology and Metabolism.


    According to Centers for Disease Control and Prevention (CDC), 30.3 million people have diabetes, or some 9.4% of the US population. Type 1 diabetes sufferers’ pancreases make very little insulin or none at all. Without insulin—the hormone that enables blood sugar to enter the cells in your body where it can be used for energy—blood sugar can’t get into cells and dangerously builds up in the bloodstream.

    “Type 1 diabetes affects about one in every 100 companion animals in the U.S., including dogs and cats, and approximately 1.25 million American children and adults,” Purdue University reports. “Because diabetes in dogs happens similarly in humans, treatment has so far been largely the same: Both need their glucose to be monitored throughout the day and insulin to be administered after meals.”

    So dogs and humans could potentially benefit from the same cure: a new set of pancreatic cells to replace the clusters of cells, called islets, that aren't releasing insulin to monitor blood glucose levels, contend researchers.



    Kelly Prinkey-Krupinski, 48 and an avid dog lover, has been struggling with adult onset Type 1 diabetes for 12 years. She said the disease runs her life. “It is a constant struggle,” she said. “My mind is always aware that every bite of food that I eat, every medicine I take, every illness and emotion I experience will affect my blood sugar. There is never a vacation from the constant balancing act to stay alive. It scares me to think of a time when I can't obtain the insulin that I must take 24-7. I would pray that there will be a cure in my lifetime. I just hate to think of the kids that struggle with Type 1 diabetes. This research with dogs sounds promising. As a dog lover myself, I would love to see if our canine friends can be cured. I'm excited to see the results.”

    “Twenty years of research and clinical trials hasn't produced an effective islet transplantation therapy because multiple donors are needed, the current method of delivering islets through the portal vein of the liver is too invasive and the human immune system tends to destroy a large percentage of transplanted islets,” the university reports.

    So Purdue researchers changed how the islets were packaged. They put them in a solution containing collagen, and injected them through the skin instead of all the way at the liver.

    "Traditionally, we transplant islets in the liver of the animal and never do it under the skin, in large part because the skin doesn't have the blood flow that the liver has for transporting insulin released by islets. And there are a lot of immune cells in the skin, so chances of rejection are high," said Raghu Mirmira, professor of pediatrics and medicine and director of the Diabetes Research Center at the Indiana University School of Medicine.

    According to the American Diabetes Association, islet transplantation can replace insulin injections and provide more physiological glucose control, but “there are not sufficient donor islets available for all the individuals who need them, and often it takes islets from several donors to transplant one recipient, exacerbating the donor shortage. A major reason for the need for multiple donors is that more than 80% of transplanted islets die within the first week after transplantation. The surviving islets may overwork and gradually die from exhaustion.”

    Researcher Qizhi Tang, PhD, at the University of California, San Francisco, is studying the changes induced in beta cells by the shortage of oxygen and nutrients. Stem cell-derived islets have a low survival rate in the first few days after transplant due to the lack of adequate oxygen and nutrient supplies. However, the American Diabetes Association states, “Evidence suggests that beta cells can be trained to survive oxygen and nutrient shortages that they are exposed to before and after transplantation.”

    The American Diabetes Association contends the promise of an unlimited source of beta cells from stem cell technology is likely to become a reality in the next several years, in an article on its site. “However, how to use this new source of cells, how these cells live and function after transplantation, and how to best control immune responses against the transplanted tissue present additional barriers to the widespread use of islet transplant. Research in these areas will be essential for the realization of the potential of stem cell derived islets for the cure of diabetes.”

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    The Purdue and IU team removed the need for transplanting in the liver by mixing mouse islets with the collagen solution. The solution solidifies upon injection just under the skin, and the body recognizes the collagen and supplies it with blood flow to exchange insulin and glucose.

    "It's minimally invasive; you don't have to go to the operating room and have this infusion into the portal vein. It's as easy as it comes, just like getting a shot," said Sherry Voytik Harbin, Purdue professor of biomedical engineering and basic medical sciences.

    As they transition to testing the formulation from mice to naturally diabetic dogs, researchers will explore the feasibility of transplanting pig islets or stem cells programmed to produce insulin, in hopes that either method will further increase donor availability, the university reports.

    The islet transplantation therapy could have implications for better treating severe pancreatitis, researchers said.

    Purdue and the IU School of Medicine collaborated on this patented work through the National Institute of Health T32 Indiana Bioengineering Interdisciplinary Training for Diabetes Research Program. The research was also supported by the National Science Foundation Graduate Research Fellowship; the Indiana University School of Medicine Center for Diabetes and Metabolic Diseases Pilot and Feasibility Program; and donations from the McKinley Family Foundation.

    Meanwhile, American Diabetes Scientist Zhen Gu, PhD, a professor in the Joint University of North Carolina/North Carolina State University Department of Biomedical Engineering, is working to develop a “smart insulin” patch that imitates the body's beta cells by both sensing blood glucose levels and releasing insulin using a nanotechnology that leverages bioengineering, biochemistry and materials science.

    The thin silicon patch – about the size of a penny – includes more than 100 microneedles, each the size of an eyelash. “The microneedles are loaded with enzymes that are able to sense blood glucose levels and trigger rapid release of insulin into the blood stream in response to high glucose,” according to the American Diabetes Association. “Dr. Gu and his colleagues have tested this technology in a mouse model of type 1 diabetes where it was able to effectively lower blood glucose levels for up to nine hours – a promising result that sets up additional pre-clinical tests (in animals) and, hopefully, eventual clinical trials (in humans).”

    The study, published in the biomedical journal, Proceedings of the National Academy of Sciences, is supported by a $1.625 million grant from the American Diabetes Association's Pathway to Stop Diabetes initiative.

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