BIO CHEMICAL EFFECT OF 1, 5-BIS (3, 5-DIMETHYLPYRAZOL-1-YL)-3- OXAPENTANE-DIA...IJSIT Editor
The present study provides evidence that 1,5-Bis (3,5-Dimethylpyrazol-1-yl)-3-oxapentane-diacetatocopper has an antidiabetic effect, as hypoglycemic agent and as antilipolytic agent, but with many abnormalities. It affected blood and liver biochemistry in rats. Sera of animals treated with 1,5-Bis(3,5-Dimethylpyrazol-1-yl)-3-oxapentane-diacetatocopper in the present study revealed a significant decrease in serum glucose and albumin, while reported a significant increase in ALT and AST. Moreover, significant decrease in body weight.
Neurotransmitters are chemicals that communicate information throughout the brain and body. Neurotransmitter synthesis is a complex process requiring the action of enzymes that are in turn dependent on the presence of specific vitamins and mineral co-factors. NeurobalanceTM is a blend of magnesium, zinc and vitamin B6, micronutrients essential to the production of serotonin, dopamine, adrenaline, noradrenaline and gamma-aminobutyric acid (GABA). This webinar will provides information relating to the therapeutic use of NeurobalanceTM and covers the following:
- A brief introduction to the Neurotransmission process
- The health implications of poor neurotransmission
- Therapeutic application of Neurobalance
- Mechanisms of action for Neurobalance
- Dosing guides for key health conditions and incorporation into protocols
BIO CHEMICAL EFFECT OF 1, 5-BIS (3, 5-DIMETHYLPYRAZOL-1-YL)-3- OXAPENTANE-DIA...IJSIT Editor
The present study provides evidence that 1,5-Bis (3,5-Dimethylpyrazol-1-yl)-3-oxapentane-diacetatocopper has an antidiabetic effect, as hypoglycemic agent and as antilipolytic agent, but with many abnormalities. It affected blood and liver biochemistry in rats. Sera of animals treated with 1,5-Bis(3,5-Dimethylpyrazol-1-yl)-3-oxapentane-diacetatocopper in the present study revealed a significant decrease in serum glucose and albumin, while reported a significant increase in ALT and AST. Moreover, significant decrease in body weight.
Neurotransmitters are chemicals that communicate information throughout the brain and body. Neurotransmitter synthesis is a complex process requiring the action of enzymes that are in turn dependent on the presence of specific vitamins and mineral co-factors. NeurobalanceTM is a blend of magnesium, zinc and vitamin B6, micronutrients essential to the production of serotonin, dopamine, adrenaline, noradrenaline and gamma-aminobutyric acid (GABA). This webinar will provides information relating to the therapeutic use of NeurobalanceTM and covers the following:
- A brief introduction to the Neurotransmission process
- The health implications of poor neurotransmission
- Therapeutic application of Neurobalance
- Mechanisms of action for Neurobalance
- Dosing guides for key health conditions and incorporation into protocols
Gluconeogenesis- Steps, Regulation and clinical significanceNamrata Chhabra
Gluconeogenesis- Thermodynamic barriers, substrates of gluconeogenesis, reciprocal regulation of glycolysis and gluconeogenesis, biological and clinical significance
The neuroprotective role of glp1 receptor aganist in people with mood disorderiWant tutor
The human body consists of a number of hormones. Each and every hormone has a different function. Like many others group of hormones, ‘Incretins’ is a group of gastrointestinal hormone which exists both in the periphery and also in the central nervous system of the human body. In the recent times it has been found that this hormonal group has varies number of functions in the human body which effects the structure and the functioning of the brain. The situations which are related to mood disorders are associated with the brain and have similar alterations and functions. The conditions which are related to mood disorders are as a result of the defects which may reflect in the form of memory, learning and other execution function (Hlscher, 2011). Such kind of defects are observed in a number of humans mainly who are having some or the other kind of metabolic disorder. Also those patients who are suffering from the mood disorders have a co-morbid metabolic conditions. This reports examines the role of GLP-1 receptor for the treatment of people who are suffering from mood disorders.
GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic po...OlgaGoryacheva4
My students Babisweta Swain, Abhishek Raj and Piyush Barwal had presented this topic in our 22nd Student Scientific Society Conference in the department of Propaedeutic of Internal Diseases No.2
1. ● Cells were scraped and spun down for protein
extraction.
● Western Blot was performed and pAKT and pGSK-3β
primary antibodies were used to probe the membranes.
Constitutively expressed heat shock protein (HSP) was
used to normalize protein concentration.
● Densitometry was performed with Image J software and
protein expression was calculated.
● This experiment was done in duplicates to have an n=4.
Experiments were performed using an adult mouse
astrocytic cell line, C8-D1A, hereby referred to in this poster
as astrocytes. The GLP-1 receptor (GLP1-R) agonist
Liraglutide was used to treat the cells.
Experiment 1
● Determine if there is a functional GLP1-R receptor on the
astrocytes
● Astrocytes were treated with 100 nM liraglutide or 100 nM
forskolin for the following times: 5, 7.5, 10, 15, 30 and 60
minutes.
● Levels of cAMP were measured using cAMP-Glo™ Max
Assay (Promega, V1681) following the manufacturer's
protocol to determine if GLP-1 was acting on GLP1-R, a
G protein-coupled receptor.
Experiment 2
● Examine the role of GLP-1 on insulin action in the
astrocytes
● The effects on insulin action were determined by studying
the phosphorylation of AKT and GSK-3β.
● The astrocytes were divided into five six-well plates.
● The cells were either treated with GLP-1, insulin, or a
combination of both.
● There were five treatment groups total: Vehicle, Insulin
alone, Insulin + GLP-1 added 18 hr. prior, Insulin + GLP-1
added 30 min. prior, and GLP-1 alone.
● 100 nM GLP-1 was given 18 hours before harvest to one
treatment group and 30 minutes before harvest to
another.
● Insulin was added 30 minutes before harvest in various
concentrations of 1 nM, 10 nM, and 100 nM.
● It appears that astrocytes express a functional GLP-1R,
suggesting the possibility that previously studied
neuroprotective effects of GLP-1 might utilize an
astrocytic mechanism
● GLP-1 was shown to act on astrocytes and mimic
insulin signaling at baseline conditions, supporting my
hypothesis
● GLP-1 was shown to enhance astrocytic insulin
signaling, supporting my hypothesis. This should
ultimately increase glycogen synthesis
● GLP-1 effects on astrocytes suggest a potential role in
attenuating insulin resistance and decreased glycogen
storage seen in stress-induced astrocytes
● Conduct the experiments in the presence of palmitate to
determine if GLP-1 can reclaim insulin signaling and
glycogen storage in stress-induced astrocytes
● Calculate actual glycogen stores in astrocytes treated
with GLP-1 to determine if GLP-1 action enhances
glycogen storage
GLP-1 acts on astrocytes to enhance insulin
signaling, providing a mechanism by which GLP-1
analogs may offer neuroprotection to patients with
diabetes-associated neurodegenerative diseases such
as Alzheimer’s.
Experiment 1: Do astrocytes express a functional
receptor for GLP-1?
● Western blot analysis indicated that our astrocyte cell
line expresses the receptor for GLP-1 and the
expression of the receptor was not altered by any of our
experimental cell treatments (data not shown).
• There is growing evidence linking type 2 diabetes (T2D)
with dementia and neurodegenerative diseases such as
Alzheimer’s disease (AD)
• The incretin hormone glucagon-like peptide 1 (GLP-1),
utilized for its insulinotropic properties in the treatment of
T2D, is also synthesized in the CNS as a neuropeptide
and has been demonstrated to have neuroprotective
effects
• Astrocytes are a type of glial cell with a central role in
neuronal health through involvement with CNS
metabolism, glycogen storage and structural support.
They are the only type of brain cells that store glycogen,
which is utilized in learning and memory
● Our lab has demonstrated in an astrocyte cell line that
glycogen synthesis is responsive to insulin. At higher
doses of insulin, these astrocytes respond with increased
glycogen storage
• To this, we have seen that palmitate (used to simulate an
obesogenic physiology) causes insulin resistance,
reduced activation via phosphorylation of protein kinase B
(AKT, a marker of insulin signaling) and lower inhibitory
phosphorylation of glycogen synthase kinase 3 beta
(GSK-3β, a negative regulator of glycogen synthesis), and
thus decreased glycogen storage in astrocytes
• This suggests that obesity or diabetes-induced disruption
of astrocytic functions may be implicated in the
pathogenesis of neurodegenerative diseases
• Little data is available about the effects of GLP-1 on glial
cell function
• OBJECTIVES: To determine if astrocytes
express a functional GLP-1 receptor and to
examine whether GLP-1 action mimics and/or
enhances insulin action on astrocytes
Methods
Background
Chris Ha, University of North Texas Health Science Center
Kevin Niswender, MD, PhD and the Niswender Laboratory
Vanderbilt University School of Medicine, Nashville, TN
Conclusion
Implications of GLP-1 for neuroprotection
Figures 3-5. GLP-1 is shown to enhance the phosphorylation of GSK-3B. This
is observed when astrocytes are treated acutely both at 30 min. as well as at 18
hours. The enhancement of insulin signaling by GLP-1 is most apparent at
10nM insulin, inducing a near maximal response.
Figures 6-8. Similar to its effects on GSK-3B, GLP-1 is also observed to enhance
the phosphorylation of AKT.
Figure 2. Liraglutide (GLP-1) treatment of astrocytes shows a time dependent
increase in cAMP levels, indicating there is a functional GLP-1R receptor.
Forskolin was used as a positive control as it stimulates adenylyl cyclase to
increase cAMP levels independent of the GLP-1 receptor
Results
Figure 1. Diagram of insulin signaling pathway
Experiment 2: What are the effects of GLP-1 on
insulin action in astrocytes?
Summary
Future Directions
Hypothesis
GLP-1 will act on astrocytes and mimic insulin action at
baseline conditions. In the presence of insulin, GLP-1
should enhance insulin action, exhibiting a mechanism
by which astrocytic glycogen storage can ultimately be
augmented.
Vehicle Palmitate
0
50
100
150
200
Concentration of Insulin (in nM)
LevelofpGSKb
Phosphorylation of Glycogen Synthase Kinase
0
3.33
10
33.3
100
333
Vehicle Palmitate
0
100
200
300
400
Treatment
LevelofpAKT
0
3.33
10
33.3
100
333
AKT Phosphorylation
Phosphorylation of
Glycogen Synthase Kinase