Human 'glucostat' identified

March 7, 2018, Karolinska Institutet

Pancreatic islets have the overall responsibility for maintaining normal blood glucose levels in the body, according to a new study by researchers at Karolinska Institutet in Sweden and the University of Miami Miller School of Medicine. The findings, published in the scientific journal Cell Metabolism, have important implications for certain diabetes treatments.

Blood levels are tightly regulated in living organism. Levels that are too low (hypoglycemia) or too high (hyperglycemia) are severe threats to health, the latter resulting in diabetes. Target glycemic levels vary between different animal species, meaning that a normal glucose concentration in mice can, for example, be considered diabetic to humans.

Exactly how glucose homeostasis is controlled is unknown, but it is known to involve several organs including the liver, the hypothalamus, and the hormone-releasing pancreatic islets, or islets of Langerhans. However, the interaction between these organs is complex, and each one of them has its own glucose set point.

"We wanted to test whether there is a leading organ or mechanism that maintains normal blood glucose levels within the characteristic narrow range in different animal species," says first author Rayner Rodriguez-Diaz, researcher at the University of Miami Miller School of Medicine, U.S., and Karolinska Institutet, Sweden. "Our hypothesis was that the glycemic set point results from the pancreatic islets working as an organ, where the hormonal output is governed by features and mechanisms intrinsic to the tissue."

To test this hypothesis, the researchers transplanted pancreatic islets from different species, including humans, into diabetic and non-diabetic mice. They then measured blood glucose levels and in the recipient mice.

"We found that the engrafted islets transferred the glycemic levels of the donor species. This indicates that the pancreatic islets have the overall responsibility for maintaining normal blood glucose levels, making them the 'glucostat' in our bodies," says principal investigator Per-Olof Berggren, Professor at the Rolf Luft Research Centre for Diabetes and Endocrinology at Karolinska Institutet's Department of Molecular Medicine and Surgery.

An interesting finding was that, in humans in contrast to rodents, the cells releasing the hormone glucagon in the pancreatic islets are of crucial importance for the regulation of insulin-producing cells, and thus the regulation of blood glucose levels.

"This means that it is imperative to use human pancreatic islets when investigating how this complex microorgan regulates under normal conditions, and why this is not functioning in diabetes," says Alejandro Caicedo, researcher at the University of Miami Miller School of Medicine. "Our findings have implications for transplantation and regenerative approaches to the treatment of diabetes, because restoring normal may require more than replacing only the insulin-producing cells."

According to the researchers, in order to cure diabetes with the help of stem cell technology in the future, it will be necessary to obtain all the cells found in the islets and then create artificial islets for transplantation.

"Furthermore, therapeutic strategies using glucagon receptor antagonists as hypoglycemic agents need to be reassessed, as they directly affect the ' ability to function as glucostats," says Professor Berggren.

Explore further: The best place to treat type 1 diabetes might be just under your skin

More information: "Paracrine interactions within the pancreatic islet determine the glycemic set point" Cell Metabolism (2018). DOI: 10.1016/j.cmet.2018.01.015

Related Stories

The best place to treat type 1 diabetes might be just under your skin

August 14, 2017
A group of U of T researchers have demonstrated that the space under our skin might be an optimal location to treat type 1 diabetes (T1D).

Young vessels rejuvenate aged insulin-producing beta cells

November 17, 2014
A recent study published in the journal PNAS shows that young capillary vessels rejuvenate aged pancreatic islets. The finding challenges prevailing views on the causes of age-dependent impaired glucose balance regulation, ...

MicroRNA-708 overexpression suppresses beta-cell proliferation

October 19, 2017
(HealthDay)—Researchers have identified a novel mechanism of glucose regulation of β-cell function and growth by repressing stress-induced microRNA-708 (miR-708), according to a study published online Oct. 2 in Diabetes.

Unique pancreatic stem cells have potential to regenerate beta cells, respond to glucose

February 27, 2018
Scientists from the Diabetes Research Institute at the University of Miami Miller School of Medicine have confirmed the existence of progenitor cells within the human pancreas that can be stimulated to develop into glucose-responsive ...

Normal insulin rhythm restored in mouse pancreas cells by glucose pulse

October 27, 2016
Pulses of the sugar glucose can restore normal insulin release in mouse pancreas cells that have been exposed to excess glucose, according to a study published in PLOS Computational Biology. This finding could improve understanding ...

Research could treat Type I Diabetes by engineering pancreatic islets outside the body

August 23, 2017
Tiny packets of cells called islets throughout the pancreas allow the organ to produce insulin. Type 1 diabetes—also known as juvenile diabetes - tricks the immune system into destroying these islets. Patients must take ...

Recommended for you

Gut hormone increases response to food

December 12, 2018
The holiday season is a hard one for anyone watching their weight. The sights and smells of food are hard to resist. One factor in this hunger response is a hormone found in the stomach that makes us more vulnerable to tasty ...

New mouse model may speed identification of promising muscular dystrophy therapies

December 12, 2018
A Massachusetts General Hospital (MGH) research team has created a new mouse model of a common form of muscular dystrophy with the potential of rapidly distinguishing promising therapeutic drugs from those unlikely to be ...

New insight into stem cell behaviour highlights therapeutic target for cancer treatment

December 12, 2018
Research led by the University of Plymouth and Technische Universität Dresden has identified a new therapeutic target for cancer treatment and tissue regeneration – a protein called Prominin-1.

Study examines disruption of circadian rhythm as risk factor for diseases

December 11, 2018
USC scientists report that a novel time-keeping mechanism within liver cells that helps sustain key organ tasks can contribute to diseases when its natural rhythm is disrupted.

New light-based technology reveals how cells communicate in human disease

December 11, 2018
Scientists at the University of York have developed a new technique that uses light to understand how cells communicate in human disease.

Researchers explore new way of killing malaria in the liver

December 8, 2018
In the ongoing hunt for more effective weapons against malaria, international researchers said Thursday they are exploring a pathway that has until now been little studied—killing parasites in the liver, before the illness ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.