The CHUM Research Centre (CRCHUM) offers a complete
range of services for studying carbohydrate and energy metabolism
in rodents. The expertise and turnkey services offered are unique
in Canada and enable basic research projects as well as evaluative
studies of the effects of compounds/drugs on carbohydrate and
energy metabolism using various tools and models in vitro and in
vivo.
Expertise:
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Carrying out research projects at the cellular
and tissue levels as well as with animal models.
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Complete metabolic phenotyping of genetically
modified rodents.
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Testing the effect of pharmacological or
molecular interventions on carbohydrate and energy metabolism in
healthy, obese and/or diabetic animal models.
For all techniques and protocols requiring the use
of rodents, standard operating procedures (SOPs) have been
established and approved by the CRCHUM’s animal care
authority: Comité Institutionnel de Protection des Animaux
(CIPA). In addition, our expertise and knowledge are at your
disposal for your experimental design needs and for preparing
protocols for CIPA approval.
All our services are turnkey. Surgeries, metabolic
tests, dosages and data analysis are performed by our
personnel.
These services are intended for researchers from
academic, hospital and industrial settings.
Services
Links with other core facilities
Rates
Information
SERVICES
Isolation of pancreatic
islets
Insulin secretion on cell lines,
isolated pancreatic islets (static or dynamic in perifusion) and in
situ pancreas
In vivo carbohydrate homeostasis
In vivo energy metabolism
Blood Biochemistry
Experimental models
Isolation of pancreatic islets
Pancreatic islets are isolated by digestion of the
pancreas following collagenase injection into the pancreatic canal.
Islets are purified by density gradient and hand-picked under a
microscope.
Insulin secretion on cell lines, isolated pancreatic
islets (static or dynamic in perifusion) and in situ
pancreas
These techniques are used to measure insulin
secretion in pancreatic beta cells in vitro and ex vivo in response
to various secretagogues (glucose, fatty acids, incretins) and/or
compounds-drugs.
In vivo carbohydrate homeostasis
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Glucose tolerance tests
This test is commonly used to establish glucose tolerance, i.e.,
the capacity for normalizing a hyperglycemic episode induced by
oral, intraperitoneal or intravenous administration of a glucose
bolus in rodents.
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Insulin tolerance tests
This test is used in rodents to determine insulin sensitivity. The
degree of hypoglycemia induced by intraperitoneal or intravenous
administration of an insulin bolus is an index of insulin
sensitivity.
Tolerance tests involve a complex metabolic response that
involves, among other things, insulin secretion and/or insulin
sensitivity. When a change in glucose tolerance or insulin
sensitivity is suspected using these tests, a quantitative analysis
of insulin secretion or insulin sensitivity can be performed using
a hyperglycemic clamp and hyperinsulinemic euglycemic clamp
respectively.
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Assessment of insulin secretion by hyperglycemic
clamp
The hyperglycemic clamp makes it possible to assess pancreatic
beta cell function, i.e., insulin secretion in response to
hyperglycemia. The clamp is performed on unrestrained, awake
animals. A glucose solution is infused at various rates by means of
an intravenous catheter to maintain hyperglycemia at 10, 15 or 20
mM (depending on the study) and monitored on blood samples
collected via an arterial catheter. During the test, various blood
samples are collected to measure plasma level of insulin and
C-peptide over time.
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Assessment of insulin sensitivity by
hyperinsulinemic euglycemic clamp
The hyperinsulinemic euglycemic clamp makes it possible to
quantitatively measure insulin sensitivity in conditions during
which glycemia and hyperinsulinemia are set at constant and
measurable levels. The clamp is performed on unrestrained, awake
animals. A glucose solution is infused simultaneously with insulin
intravenously in order to maintain glycemia at a target value
(depending on the study). The amount of infused glucose needed to
maintain glycemia during a hyperinsulinemic condition is a direct
measure of insulin sensitivity.
In vivo energy metabolism
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Body composition
The ECHO MRI is used to measure rodents’ body composition.
Fat mass, lean mass, free liquids and total water are measured in
less than a minute on awake animals, thereby facilitating
longitudinal monitoring of body composition.
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Metabolic cages
The Accu Scan system is used to non-invasively measure food intake
and voluntary locomotive activity in rodents, as well as their
oxygen consumption and carbon dioxide production, thereby
establishing respiratory quotient and index of use of glucose and
lipid substrates.
The Comprehensive Lab Animal Monitoring System (CLAMS) is used for
simultaneous and non-invasive measurements in rodents of food
intake, water consumption, energy expenditure, respiratory quotient
and voluntary locomotive activity.
Blood Biochemistry
We provide various dosages for metabolites (glucose, fatty
acids, triglycerides, lipoproteins), hormones (insulin, C-peptide,
GLP-1) and cytokines (leptin, IL1, IL6) from plasma or serum
samples.-Experimental models.
Experimental models
We provide several models of obesity (high fat
diet, obese Zucker rat) and/or diabetes (pancreatectomy,
streptozotocin injection, Goto-Kakizaki rat, db/db obese mouse). In
addition, a model of chronic glucose and/or lipid systemic infusion
is also available.
LINKS WITH OTHER FACILITIES
Our services are complementary to services offered by the
CRCHUM’s cardiovascular core facility, the Centre for
Ecogenomic Models of Human Diseases, and its behaviour core
facility, making it possible to conduct multidisciplinary research
projects.
INFORMATION
For more information about our services, please contact the
facility manager:
Thierry Alquier
pheno.metabolique@crchum.qc.ca
(514) 890-8000, ext: 26181