Signal Transduction – Ismael Valladolid Acebes' research group

Research Areas

The coupling of glucose metabolism to electrical activity remains central in all models of beta-cell stimulus-secretion coupling. The resting membrane potential of the beta-cell is set by the ATP-sensitive potassium (KATP) channel. Incubation of the pancreatic beta-cell with stimulatory glucose concentrations leads to the activation of a cascade of reactions which ends in the exocytosis of stored insulin. This complex of processes starts with the uptake of glucose by the beta-cell high-Km/low affinity glucose transporter GLUT2 and proceeds with the conversion of glucose into glucose-6-phosphate by the beta-cell isoform of glucokinase. Metabolism of glucose in glycolysis and the Krebs cycle results in the generation of ATP. Elevation in the ATP/ADP ratio leads to closure of the KATP, which in turn results in depolarization of the plasma membrane.

The subsequent opening of voltage-gated L-type Ca²⁺ channels leads to an increase in the cytoplasmic free Ca²⁺ concentration, [Ca²⁺]i, which promotes insulin secretion. With regard to the actions of the plethora of additional factors like neurotransmitters, islet generated factors and systemic growth factors; they are in most cases mediated by membrane receptors coupled to either G-proteins or tyrosine kinases, many of which subsequently activate the phosphoinositide-derived second messenger cascades. Among other things, the role of signalling through these receptor-operated effector systems is the focus of our work.

Pancreatic beta-cell signal transduction is complex and involves a well-regulated interaction of a number of signals generated by the metabolism of glucose and the activation of a variety of receptor-operated pathways. Our future research will tell to what extent these various signalling pathways are really regulatory pathways under in vivo conditions or rather serve as signalling pathways maintaining normal beta-cell function.

Subgroups

News Signal Transduction

Researchers use the eye as a window to study liver health
1 February, 2024
Researchers at Karolinska Institutet have developed a method to study liver function and disease without requiring invasive procedures. After transplanting liver cells into the eye of mice, the cornea can be used as a window into the body to monitor liver health over time. The study is published in the journal Nature Communications.

Eye implant may be used to treat diabetes
18 October, 2023
Researchers at Karolinska Institutet and KTH Royal Institute of Technology have developed a microscale device for implantation in the eye, which presents new opportunities for cell-based treatment of diabetes and other diseases. The study is published in the journal Advanced Materials.

New strategy to preserve insulin-producing cells in diabetes
30 March, 2022
High blood glucose is responsible for several complications in type 1 and type 2 diabetes. Researchers at Karolinska Institutet have identified a new antidiabetic substance that preserves the activity of insulin-producing beta cells and prevents high blood glucose in mice. The study is published in the journal Science Translational Medicine.

The Crown Princess visits Rolf Luft Research Center at MMK
22 November, 2021
On November 9, 2021, the Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, was visited by the Crown Princess Victoria. Ongoing research on diabetes was presented to her and a visit to the laboratory was also included.

Could islet transplantation to the eye help stabilise the glucose levels of people with type 1 diabetes?
28 September, 2021
Led by Professor Per-Olof Berggren at Karolinska Institutet in Sweden, a Phase 1 clinical trial is intended to reveal whether islet transplantation to the anterior eye chamber of people with type 1 diabetes could help restore insulin secretion to maintain glucose levels. The Novo Nordisk Foundation has awarded Karolinska Institutet up to DKK 10 million for the project.

Metabolic derangements caused by a high-fat diet may be possible to eliminate
12 March, 2021
Intake of a high-fat diet leads to an increased risk for obesity, type 2 diabetes, cardiovascular diseases and fatty liver. A study in mice from Karolinska Institutet shows that it is possible to eliminate the deleterious effects of a high-fat diet by lowering the levels of apolipoprotein CIII (apoCIII), a key regulator of lipid metabolism. The study is published in the journal Science Advances.

Findings about hair-like structures on cells inside vessels may be relevant for diabetes treatment
4 December, 2020
A new study from Karolinska Institutet and the Helmholtz Diabetes Research Center shows that primary cilia, hair-like protrusions on endothelial cells inside vessels, play an important role in the blood supply and delivery of glucose to the insulin-producing beta cells in the pancreatic islets. The findings are published in eLife and may be relevant for transplantation therapies in diabetes, as formation of functional blood vessels is important for the treatment to be successful.

KI receives over SEK 440 million from Swedish Research Council for medical research
9 November, 2020
The Swedish Research Council has awarded five-year grants totalling SEK 442,680,000 to 110 researchers at Karolinska Institutet. All in all, the SRC is awarding almost SEK 1 billion to 247 researchers in the fields of medicine and health.

Calcium channels play a key role in the development of diabetes
23 December, 2019
Researchers at Karolinska Institutet have deciphered the diabetogenic role of a certain type of calcium channel in insulin-secreting beta cells. The researchers believe that blockade of these channels could be a potential new treatment strategy for diabetes. The study is published in the scientific journal PNAS.

New clues to the link between ALS and type 2 diabetes
9 December, 2019
Patients with ALS (amyotrophic lateral sclerosis) often suffer from type 2 diabetes. This phenomenon has since long remained mechanistically enigmatic. Now, researchers at Karolinska Institutet in Sweden have identified a molecular mechanism linking these two diseases. The study is published in the scientific journal PNAS.

New eye monitoring system developed to monitor islet transplantation
26 November, 2019
A collaboration between Professor Per-Olof Berggren from the group Signal Transduction and researchers in the Republic of Korea has led to the development of a soft, smart contact lens to monitor the intraocular pressure and applied it for noninvasive monitoring in association with the intraocular islet transplantation in diabetes.

Multimillion grant from SSF
5 September, 2019
Two researchers at Karolinska Institutet, Per-Olof Berggren and Birgitta Henriques-Normark, receive a total of SEK 68 million in grants from the Swedish Foundation for Strategic Research, SSF. The Med-X research program is an interdisciplinary initiative in medicine and technical science. The purpose is to provide new solutions for clinical needs.

Novel findings explain indirect regulation of glucose homeostasis
16 August, 2019
The hormone secreting part of the pancreas, the islets of Langerhans, has a unique cyto-architecture that allows functional interrelationships between the different cell types. Somatostatin is secreted by the delta cell and is an effective inhibitor of the insulin secreting beta cell and the glucagon secreting alpha cell. According to a novel study from Karolinska Institutet, published in the journal Nature Communications, the delta cell can thereby indirectly affect glucose homeostasis.

Transplanted cells reveal early signs of type 1 diabetes
15 May, 2019
By the time type 1 diabetes is diagnosed, most of the insulin-producing beta cells have already been destroyed. Now, using an innovative transplantation technique, researchers at Karolinska Institutet and University of Miami Miller School of Medicine have been able to intervene to save the beta cells in mice by discovering early signs of the disease. The study is published in Diabetologia, the scientific journal of the European Association for the Study of Diabetes (EASD).

ERC grant for research on insulin-producing cells
28 March, 2019
The ERC Advanced Grant is one of the most prestigious funding programmes for research in Europe. Per-Olof Berggren, professor of experimental endocrinology at Karolinska Institutet, is now awarded this grant for the second time.

Per-Olof Berggren elected member of the Korean Academy of Science and Technology
31 May, 2018
Per-Olof Berggren, Professor of Experimental Endocrinology and Research Group Leader of the group Signal Transduction at the Department of Molecular Medicine and Surgery has been elected member of the Korean Academy of Science and Technology, KAST.

The body’s “glucostat” identified
06 Mar 2018
It is the pancreatic islets that have the overall responsibility for maintaining normal blood glucose levels in our bodies, according to a new study by researchers at Karolinska Institutet in Sweden and the University of Miami Miller School of Medicine, USA. The findings, published in the...

Method developed that gives researchers better conditions for studying insulin-producing cells
09 Aug 2017
Researchers have established a unique method enabling them to study the function of insulin-producing cells under conditions that are similar to those in humans. This can pave the way to development of new medicines for the treatment of diabetes. Beta cells in the pancreas produce the hormone...

KI professor shares award with historical celebrities
18 Apr 2017
Per-Olof Berggren, professor of experimental endocrinology at KI, has been elected member of the American Academy of Arts & Science. He share this distinguished award with historical celebrities, such as Albert Einstein, Winston Churchill and Nelson Mandela. Professor Per-Olof Berggren is a...

Per-Olof Berggren appointed Distinguished Professor in Italy
24 Oct 2016
Professor Per-Olof Berggren has been appointed Distinguished Professor at the University of Rome Tor Vergata, Italy. Per-Olof Berggren , Professor of Experimental Endocrinology and Research Group Leader of the group Signal Transduction at the Department of Molecular Medicine and Surgery. Research...

Professor Per-Olof Berggren elected member of the National Academy of Medicine
18 Oct 2016
Per-Olof Berggren , Professor of Experimental Endocrinology at the Department of Molecular Medicine and Surgery, Karolinska Institutet, has been elected as member of the National Academy of Medicine, NAM. The National Academy of Medicine announced the election of 70 U.S. members and 9 international...

New non-invasive method for studying the development of insulin-producing cells
04 Apr 2016
Researchers at Karolinska Institutet and Nanyang Technological University in Singapore have produced a unique method for monitoring the development of insulin-producing cells, which play a key part in regulating blood glucose concentration. The method, which is described in the journal Diabetologia...

Insulin-secreting cells report on insulin resistance
22 Feb 2016
Diabetes researchers at Karolinska Institutet have developed a novel technique that makes it possible to monitor insulin resistance in a non-invasive manner over time in mice. The new method, presented in the journal Scientific Reports , can be used to assess insulin resistance during progression...

Type 2 diabetes drug can exhaust insulin-producing cells
12 Feb 2016
Long-term use of liraglutide, a substance that helps to lower blood sugar levels in patients with type 2 diabetes, can have a deteriorating effect on insulin-producing beta cells, leading to an increase in blood sugar levels. This according to a study on mice implanted with human insulin-producing...

Novel mechanism of insulin resistance in type 2 diabetes
17 Sep 2015
Insensitivity to insulin, also called insulin resistance, is associated with type 2 diabetes and affects several cell types and organs in the body. Now, scientists from Sweden’s Karolinska Institutet have discovered a mechanism that explains how insulin-producing cells can be insulin resistant and...

New knowledge about how type 2 diabetes develops
19 May 2015
An international research team, led from Sweden’s Karolinska Institutet, have presented new knowledge about what happens when type 2 diabetes develops. By studying the insulin-producing beta cells in mice in real time, they have managed to identify a key part of the process that leads to the death...

Young vessels rejuvenate aged insulin-producing beta cells
18 Nov 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, a condition that often develops into diabetes type 2. The international...

Study explains the link between cilia and diabetes
06 Nov 2014
Tiny extensions on cells, cilia, play an important role in insulin release, according to a new study, which is published in Nature Communications . The researchers report that the cilia of beta cells in the pancreas are covered with insulin receptors and that changed ciliary function can be...

Mechanism behind age-dependent diabetes discovered
17 Sep 2014
Ageing of insulin-secreting cells is coupled to a progressive decline in signal transduction and insulin release, according to a recent study by researchers at Karolinska Institutet in Sweden. The finding, which is published in the journal Diabetes , provides a new molecular mechanism underlying...

KI researchers win Wallenberg Scholarship
12 Dec 2012
The Wallenberg Scholars programme supports and stimulates some of the most successful researchers at Swedish universities. Two researchers at Karolinska Institutet have now been awarded SEK 15 million each to be divided over a period of five years. Per-Olof Berggren Per-Olof Berggren, professor of...

Prizes awarded for diabetes and metabolism research
19 Sep 2012
Two researchers at Karolinska Institutet are to be rewarded for their scientific achievements, which are potentially of major significance to the treatment of diseases such as type II diabetes. Professor Per-Olof Berggren receives the Axel Hirsch Prize for his discoveries on insulin release in the...

Signal Transduction – Ismael Valladolid Acebes' research group

Research Areas

Staff and contact

Group leader

All members of the group

Publications

Publication List, pdf

News Signal Transduction

Associated International Labs

Signal Transduction – Ismael Valladolid Acebes' research group

News Signal Transduction

Calendar Signal Transduction

Signal Transduction Research group

Research Areas

Subgroups

Insulin Receptor Signalling

Inositide Signalling

Voltage-gated Calcium Channels

Intracellular Calcium Oscillations

Stress Signalling

Serum Factors

Pancreatic Islet Plasticity

Staff and contact

Group leader

All members of the group

Publications

Links

Publication List, pdf

News Signal Transduction

Associated International Labs