Abstract
Aims/hypothesis: Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods: We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results: Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation: These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.
| Original language | English |
|---|---|
| Pages (from-to) | 965-978 |
| Number of pages | 14 |
| Journal | Diabetologia |
| Volume | 54 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2011 |
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Keywords
- Anti-inflammatory effect
- Diabetic nephropathy
- Exendin-4
- Glomerular endothelial cells
- GLP-1 receptor agonist
- Intercellular adhesion molecule-1
- Macrophage
- Nuclear factor-κB
- Type 1 diabetic rats
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes. / Kodera, R.; Shikata, Kenichi; Kataoka, Hitomi; Takatsuka, T.; Miyamoto, Satoshi; Sasaki, M.; Kajitani, N.; Nishishita, S.; Sarai, K.; Hirota, D.; Sato, C.; Ogawa, D.; Makino, Hirofumi.
In: Diabetologia, Vol. 54, No. 4, 04.2011, p. 965-978.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes
AU - Kodera, R.
AU - Shikata, Kenichi
AU - Kataoka, Hitomi
AU - Takatsuka, T.
AU - Miyamoto, Satoshi
AU - Sasaki, M.
AU - Kajitani, N.
AU - Nishishita, S.
AU - Sarai, K.
AU - Hirota, D.
AU - Sato, C.
AU - Ogawa, D.
AU - Makino, Hirofumi
PY - 2011/4
Y1 - 2011/4
N2 - Aims/hypothesis: Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods: We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results: Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation: These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.
AB - Aims/hypothesis: Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods: We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results: Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation: These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.
KW - Anti-inflammatory effect
KW - Diabetic nephropathy
KW - Exendin-4
KW - Glomerular endothelial cells
KW - GLP-1 receptor agonist
KW - Intercellular adhesion molecule-1
KW - Macrophage
KW - Nuclear factor-κB
KW - Type 1 diabetic rats
UR - http://www.scopus.com/inward/record.url?scp=79953826349&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953826349&partnerID=8YFLogxK
U2 - 10.1007/s00125-010-2028-x
DO - 10.1007/s00125-010-2028-x
M3 - Article
C2 - 21253697
AN - SCOPUS:79953826349
VL - 54
SP - 965
EP - 978
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 4
ER -