Abstract
Using knockout and transgenic technology, genetically modified animal models allowed us to understand the role of glucagon signalling in metabolism. Mice with a global deletion of the glucagon receptor gene (Gcgr) were designed using gene targeting. The phenotype of Gcgr-/-mouse provided important clues about the role of Gcgr in foetal growth, pancreatic development and glucose and lipid homeostasis. The lack of Gcgr activation was associated with: (i) hypoglycaemic pregnancies, poor foetal growth and increased foetal-neonatal demise; (ii) altered cytoarchitecture of pancreatic islets; (iii) altered glucose, lipid and hormonal milieu; (iv) reduced gastric emptying; (v) altered body composition and protection from diet-induced obesity; (vi) altered energy state; (vii) impaired hepatocyte survival; (viii) altered metabolic response to prolonged fasting and exercise and (ix) prevented development of diabetes in insulin-deficient mice. In contrast, mice overexpressing the Gcgr on pancreatic β-cells displayed an increase insulin secretion, pancreatic insulin content and β-cell mass, and partially protected against hyperglycaemia and impaired glucose tolerance when fed a high-fat diet. These findings suggest that glucagon signalling plays a significant role in the regulation of glucose and lipid homeostasis. Treatment options designed to block Gcgr activation may have negative implications in the treatment of diabetes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 144-150 |
| Number of pages | 7 |
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 13 |
| Issue number | SUPPL. 1 |
| DOIs | |
| State | Published - Oct 2011 |
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Keywords
- Diabetes
- Gcgr knockout mouse model
- Glucagon
- Glucagon signalling
- Hypoglycaemia
- Islets
- Pancreas
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Novel insight into glucagon receptor action : Lessons from knockout and transgenic mouse models. / Vuguin, P. M.; Charron, Maureen J.
In: Diabetes, Obesity and Metabolism, Vol. 13, No. SUPPL. 1, 10.2011, p. 144-150.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel insight into glucagon receptor action
T2 - Lessons from knockout and transgenic mouse models
AU - Vuguin, P. M.
AU - Charron, Maureen J.
PY - 2011/10
Y1 - 2011/10
N2 - Using knockout and transgenic technology, genetically modified animal models allowed us to understand the role of glucagon signalling in metabolism. Mice with a global deletion of the glucagon receptor gene (Gcgr) were designed using gene targeting. The phenotype of Gcgr-/-mouse provided important clues about the role of Gcgr in foetal growth, pancreatic development and glucose and lipid homeostasis. The lack of Gcgr activation was associated with: (i) hypoglycaemic pregnancies, poor foetal growth and increased foetal-neonatal demise; (ii) altered cytoarchitecture of pancreatic islets; (iii) altered glucose, lipid and hormonal milieu; (iv) reduced gastric emptying; (v) altered body composition and protection from diet-induced obesity; (vi) altered energy state; (vii) impaired hepatocyte survival; (viii) altered metabolic response to prolonged fasting and exercise and (ix) prevented development of diabetes in insulin-deficient mice. In contrast, mice overexpressing the Gcgr on pancreatic β-cells displayed an increase insulin secretion, pancreatic insulin content and β-cell mass, and partially protected against hyperglycaemia and impaired glucose tolerance when fed a high-fat diet. These findings suggest that glucagon signalling plays a significant role in the regulation of glucose and lipid homeostasis. Treatment options designed to block Gcgr activation may have negative implications in the treatment of diabetes.
AB - Using knockout and transgenic technology, genetically modified animal models allowed us to understand the role of glucagon signalling in metabolism. Mice with a global deletion of the glucagon receptor gene (Gcgr) were designed using gene targeting. The phenotype of Gcgr-/-mouse provided important clues about the role of Gcgr in foetal growth, pancreatic development and glucose and lipid homeostasis. The lack of Gcgr activation was associated with: (i) hypoglycaemic pregnancies, poor foetal growth and increased foetal-neonatal demise; (ii) altered cytoarchitecture of pancreatic islets; (iii) altered glucose, lipid and hormonal milieu; (iv) reduced gastric emptying; (v) altered body composition and protection from diet-induced obesity; (vi) altered energy state; (vii) impaired hepatocyte survival; (viii) altered metabolic response to prolonged fasting and exercise and (ix) prevented development of diabetes in insulin-deficient mice. In contrast, mice overexpressing the Gcgr on pancreatic β-cells displayed an increase insulin secretion, pancreatic insulin content and β-cell mass, and partially protected against hyperglycaemia and impaired glucose tolerance when fed a high-fat diet. These findings suggest that glucagon signalling plays a significant role in the regulation of glucose and lipid homeostasis. Treatment options designed to block Gcgr activation may have negative implications in the treatment of diabetes.
KW - Diabetes
KW - Gcgr knockout mouse model
KW - Glucagon
KW - Glucagon signalling
KW - Hypoglycaemia
KW - Islets
KW - Pancreas
UR - http://www.scopus.com/inward/record.url?scp=79961176667&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79961176667&partnerID=8YFLogxK
U2 - 10.1111/j.1463-1326.2011.01447.x
DO - 10.1111/j.1463-1326.2011.01447.x
M3 - Article
C2 - 21824268
AN - SCOPUS:79961176667
VL - 13
SP - 144
EP - 150
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - SUPPL. 1
ER -