Nav: Home

A sustained and controllable insulin release system

February 27, 2017

The prevalence of diabetes has grown around the world over the past three decades. In 2016, the World Health Organization estimated that 422 million people had the disease as the rate of obesity also increased. Aside from proper diet and exercise, the best treatment for diabetes is the delivery of insulin into the body that is both controllable and sustainable over time to manage blood glucose levels. Working toward the development of a better insulin delivery system, a research group from Kumamoto University in Japan has been experimenting with polyethylene glycol (PEG) modification (PEGylation) of protein drugs through a host-guest interaction between cyclodextrin (CyD) and adamantane to improve the stability and lifetime of insulin, calling the results of their work "SPRA technology". Their current research focuses on combining SPRA technology with another development of their own that allows for better control of insulin release, "polypseudorotaxane (PPRX) technology". Their goal in combining the two technologies was to develop a sustained and controllable insulin release system.

Using mono- or multi-SPRA-insulin solutions and alpha- or gamma-cylodextrin (CyD), the researchers developed four types of SPRA-insulin/CyD PPRXs, mono-SPRA-insulin/alpha-CyD, mono-SPRA-insulin/gamma-CyD, multi-SPRA-insulin/alpha-CyD, and multi-SPRA-insulin/gamma-CyD PPRX. Alpha-CyDs were found to form PPRXs with a single PEG molecule of SPRA-insulin, whereas gamma-CyD formed them with two molecules. The multi-SPRA-insulin was expected to remain in the blood supply for a relatively long period of time, and the use of different concentrations of CyDs allowed researchers to control insulin release through the CyD and PEG equilibrium reaction.

The hypoglycemic effects of the insulin type with the highest CyD safety profile (multi/gamma) was then assessed in vivo. Two gamma-CyD concentrations, 116 mg/ml and 232 mg/ml, of multi-SPRA-Insulin/gamma-CyD PPRX were tested against a control of multi-SPRA-insulin. "We found that 232 mg/ml gamma-CyD PPRX provided for a longer blood glucose reduction time than the 116 mg/ml PPRX and the control. This is quite important since it shows that both sustained and controlled insulin release can be achieved, which is necessary for the treatment of diabetes," said lead researcher Dr. Hidetoshi Arima. "Furthermore, a blood chemistry safety analysis of creatinine, blood urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were found to be unchanged by the insulin injections. Our SPRA-PPRX injections appear to be a safe and reliable insulin release system."

A limitation of this study is the low number of experimental subjects, only 3 rats per group. Also, it was unclear whether or not a diabetic animal model was used in the experiments.

In future work, the researchers plan to combine other forms of insulin with gamma-CyD PPRX with the hope of further improving diabetes treatment. The current findings be found online in the journal Carbohydrate Polymers at ScienceDirect.com.
-end-
[Reference]

T. Hirotsu, T. Higashi, K. Motoyama, and H. Arima, "Cyclodextrin-based sustained and controllable release system of insulin utilizing the combination system of self-assembly PEGylation and polypseudorotaxane formation," Carbohydrate Polymers, vol. 164, pp. 42-48, Jan. 2017. DOI: 10.1016/j.carbpol.2017.01.074

Kumamoto University

Related Diabetes Articles:

The role of vitamin A in diabetes
There has been no known link between diabetes and vitamin A -- until now.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
New cause of diabetes
Although insulin-producing cells are found in the endocrine tissue of the pancreas, a new mouse study suggests that abnormalities in the exocrine tissue could cause cell non-autonomous effects that promotes diabetes-like symptoms.
The Lancet Diabetes & Endocrinology: Reducing sugar content in sugar-sweetened drinks by 40 percent over 5 years could prevent 1.5 million cases of overweight and obesity in the UK and 300,000 cases of diabetes
A new study published in The Lancet Diabetes & Endocrinology journal suggests that reducing sugar content in sugar sweetened drinks (including fruit juices) in the UK by 40 percent over five years, without replacing them with any artificial sweeteners, could prevent 500,000 cases of overweight and 1 million cases of obesity, in turn preventing around 300,000 cases of type 2 diabetes, over two decades.
Breastfeeding lowers risk of type 2 diabetes following gestational diabetes
Women with gestational diabetes who consistently and continuously breastfeed from the time of giving birth are half as likely to develop type 2 diabetes within two years after delivery, according to a study from Kaiser Permanente published today in Annals of Internal Medicine.

Related Diabetes Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...