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Printable Handouts
Navigable Slide Index
- Introduction
- Innate immunity senses metabolic disturbance
- Glucose induces beta-cell apoptosis in P.obesus
- Glucose induces IL-1-beta release from islets
- Hyperglycemia induced IL-1-beta production
- Endogenous production of IL-1Ra
- High production of IL-1R in islet cells
- Decreased functional beta-cell mass in T2D
- Immune cell infiltration
- Islet inflammation in T2D (1)
- Islet inflammation in T2D (2)
- IL-1Ra reduces islet inflammation
- IL-1Ra reduces islet immune cell infiltration
- Islet inflammation in T2D (3)
- Mechanistic overview up till now
- IL-1-Ra study
- Anakinra study (1)
- Anakinra study (2)
- Anakinra study (3)
- IL-1 inhibition improves beta-cell function
- Studies of IL-1 antagonism in type 2 diabetes
- Improved insulin secretion in non-diabetic subjects
- IL-1-beta antagonists presented in meetings
- Canakinumab administration in T2D patients
- Treatment with LY-2189102
- Effects of gevokizumab on glycemia and T2D
- The IL-1 system and insulin resistance
- CANTOS study
- IL-6
- Exercise-induced GLP-1 is IL-6 dependent
- IL-6 improves oral glucose tolerance
- Our hypothesis
- IL-6 improves beta cell function in obese mice
- IL-6 elevation improves glucose homeostasis
- IL-6 elevation increases GLP-1 synthesis
- Proglucagon processing
- IL-6 increases GLP-1 in human alpha cells
- HF diet increases GLP-1 and PC1/3 in alpha cells
- Summary
Topics Covered
- Mechanisms of insulin secretion defect in type 2 diabetes
- Islet inflammation in type 2 diabetes
- Role of IL-1beta and inflammasome in type 2 diabetes
- Treatment of type 2 diabetes
- IL-6 and GLP-1
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Donath, M.Y. (2013, May 22). Inflammation and type 2 diabetes [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 1, 2024, from https://doi.org/10.69645/KGXL2243.Export Citation (RIS)
Publication History
Financial Disclosures
- Marc Donath is listed as the inventor on a patent filed in 2003 for the use of an IL-1 receptor antagonist for the treatment or prevention of type 2 diabetes.
A selection of talks on Cell Biology
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Marc Donath,
and I'm going to
present a talk on
"Inflammation in
Type 2 Diabetes".
0:11
The basic concept is that the
innate immune system has a
sub-specialization
which is able to
recognize dangers that come
from metabolic stress.
The idea is that in
the same way as the
innate immune system is
recognizing specific patterns of
virus or microbes or bacteria,
in the same way the
innate immune system
has the ability to sense
metabolic stress and then to
respond to it in a
very specific manner.
0:47
I will now continue on
showing you how we came to
this concept and how this
translates into diabetes.
Our initial study
was done in the
Psamommys obesus, an
animal model of diabetes,
where we observed that glucose
itself can induce an
apoptotic process.
As you can see in this slide,
increasing glucose concentration
induces apoptosis in
the Beta cells which are labeled
in black when they
become apoptotic.
1:20
Next, we were wondering
how this glucose
induces apoptosis,
and then we observed
that glucose induces
cytokine IL-1 Beta
by metabolic stress.
Increasing glucose concentration,
as we can see here,
induces a release of IL-1 Beta,
in the human islets.
We did a lot of control to
this study showing that this is
a specific response of the islet
so for example the metabolically
inactive L-glucose which
induces also an osmotic
pressure did not
induce the IL-1 Beta release.