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Expression of miR-200c in human pancreatic islets and the effect of overexpression on insulin secretion A: Expression of miR-200a, miR-200b and miR-200c in ND and T2D donor islet cells
.
Data are presented as mean ± SEM
.
*P < 0.05 for N = 25 ND donors and N = 9 T2D donors
.
B: Expression of miR-200c in EndoC-βH1β cells after overexpression of miR-200c (OE200c) compared with scramble control (SCR)
.
C: Insulin released by EndoC-βH1 cells after 1 hour stimulation with low glucose (1mmol/L [1G]) or high glucose (20mmol/L [20G])
.
Secretion measurements were performed by transfecting cells containing control (SCR) and pre-miR-200c (OE200C) plasmids as indicated
.
D: Depolarization-induced insulin secretion (50 mmol/LK+ in SCR and OE200c endogenous c-βH1β cells.
Data in BD are presented as mean ± SEM of N = 6 biological replicates
.
*P < 0.05, ***P < 0.001 vs.SCR, ***P < 0.01 vs. hypoglycemia, using Student's paired t-test and ANOVA.
DOI: 10.2337/db21-0077
.
Data are presented as mean ± SEM
.
*P < 0.05 for N = 25 ND donors and N = 9 T2D donors
.
B: Expression of miR-200c in EndoC-βH1β cells after overexpression of miR-200c (OE200c) compared with scramble control (SCR)
.
C: Insulin released by EndoC-βH1 cells after 1 hour stimulation with low glucose (1mmol/L [1G]) or high glucose (20mmol/L [20G])
.
Secretion measurements were performed by transfecting cells containing control (SCR) and pre-miR-200c (OE200C) plasmids as indicated
.
D: Depolarization-induced insulin secretion (50 mmol/LK+ in SCR and OE200c endogenous c-βH1β cells.
Data in BD are presented as mean ± SEM of N = 6 biological replicates
.
*P < 0.05, ***P < 0.001 vs.SCR, ***P < 0.01 vs. hypoglycemia, using Student's paired t-test and ANOVA.
DOI: 10.2337/db21-0077
Researchers at Lund University have found that people with type 2 diabetes have increased levels of a microRNA that negatively affects insulin secretion
.
Their experiments with insulin-producing cells in the human pancreas also showed that insulin secretion could be increased by reducing levels of this microRNA
.
An important goal of this research is to develop new treatments for people living with the disease
.
In type 2 diabetes, the ability of the pancreas to produce and release insulin is impaired
.
Previous studies have shown that microRNAs are involved in this exacerbation process
.
MicroRNAs are noncoding RNAs that regulate the number of genes and proteins in cells
.
Reducing the amount of microRNA could be a treatment for people with type 2 diabetes
.
The study showed that a microRNA called miR-200c appeared to affect insulin secretion in diabetic mice
.
Until now, little is known about the role of miR-200c in human insulin secretion
.
"Our study shows that miR-200c levels differ between patients and non-patients,
" says Lena Eliasson, corresponding author of the study and a diabetes researcher at the Lund University Diabetes Center (LUDC)
.
The study is published in the scientific journal Diabetes on
.
increase insulin secretion
They measured miR-200c in 34 Langerhans' dead donor islets with type 2 diabetes and non-type 2 diabetes, and showed elevated levels of miR-200c in patients with type 2 diabetes
.
To determine if it was possible to increase insulin secretion by reducing the levels of miR-200c in cells, the researchers also performed experiments on Langerhans islands from deceased type 2 diabetes donors
.
The result of the experiment was increased insulin secretion from the islets of Langerhans in the three donors
.
"Across all donors, this number has roughly tripled
.
We would have liked to do this experiment with more donors, but it was difficult to find material for new donations
.
We are of course very grateful to the donors, who have Contributing to the study in a way
.
It is important to understand what happens to insulin secretion and how it is regulated in humans in order to develop new treatments," said one of the study's lead authors, Diabetes at LUDC.
and epigenetics researcher Jones Ofori said
.
improved treatment
The researchers behind the study plan to confirm their results in diabetic rats to better understand what happens to insulin secretion when they reduce miR-200c levels
.
An important research goal is to develop new treatments for type 2 diabetes
.
Previous research at the Lund University Diabetes Center has shown that diabetes can be divided into subgroups based on disease progression, with some patients having more problems with insulin secretion than others
.
“Current treatment options for type 2 diabetes are not optimal for everyone
.
Several studies suggest that more individualized treatment of type 2 diabetes is needed
.
For us, targeting people with severely impaired insulin secretion Treatment could be an interesting thing
.
In the long run, we hope our research will lead to treatments that better control blood sugar levels," said Lena Eliasson
.
The research team is currently working on a mapping effort to map microRNAs that may be involved in insulin secretion in type 2 diabetes
.
This knowledge is important for the development of precision therapy
.
"In our microRNA map, we can see that miR-200c is a strong candidate for targeted therapy, which has also emerged in other studies
.
A challenge before us is to develop a drug that only affects Langerhans insulin treatment of islets without affecting other tissues," said Lena Eliasson, Professor of Experimental Diabetes Research at Lund University
.
Human Tissue Laboratory
The study was performed on islets donated to the Human Tissue Laboratory (HTL), an important biobank for diabetes research that has been established as part of the Swedish Strategic Research Area of Excellence in Diabetes Research (EXODIAB)
.
HTL collects insulin-producing cells, as well as the body's liver, muscle and adipose tissue
.
The biobank stores blood samples, urine and stool samples, and information about individuals and their medical history
.
HTL was established in collaboration between Lund University and Uppsala University, which are part of the EXODIAB research collaboration project
.
MicroRNAs and islets of Langerhans Island
MicroRNAs are small, noncoding RNA molecules that regulate protein production
.
A single microRNA can regulate many proteins in a cell or signaling pathway
.
MicroRNAs are involved in the development of type 2 diabetes and the ability of the pancreas to secrete insulin
.
The islets of Langerhans mainly contain insulin-producing cells and glucagon-producing cells
.
These hormones regulate blood sugar and metabolism
.
Langerhans Island is difficult to study due to its inaccessible location
.