Abstract
Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARα by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n = 8; db/m, n = 6) or a diet containing fenofibrate (db/db, n = 8; db/m, n = 7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P < 0.001) and HbA1c levels (P < 0.001), and was associated with decreased food intake (P < 0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P < 0.001) and reduced plasma insulin levels (P < 0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P < 0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P < 0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARα, decreased type I collagen production. Taken together, the PPARα agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARα by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.
| Original language | English |
|---|---|
| Pages (from-to) | 1511-1517 |
| Number of pages | 7 |
| Journal | Kidney International |
| Volume | 69 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2006 May 1 |
| Externally published | Yes |
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Keywords
- Diabetic nephropathy
- Fenofibrate
- PPARα
- Type II diabetes
ASJC Scopus subject areas
- Nephrology
Cite this
PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic. / Park, C. W.; Zhang, Y.; Zhang, X.; Wu, J.; Chen, L.; Cha, Dae-Ryong; Su, D.; Hwang, M. T.; Fan, X.; Davis, L.; Striker, G.; Zheng, F.; Breyer, M.; Guan, Y.
In: Kidney International, Vol. 69, No. 9, 01.05.2006, p. 1511-1517.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic
AU - Park, C. W.
AU - Zhang, Y.
AU - Zhang, X.
AU - Wu, J.
AU - Chen, L.
AU - Cha, Dae-Ryong
AU - Su, D.
AU - Hwang, M. T.
AU - Fan, X.
AU - Davis, L.
AU - Striker, G.
AU - Zheng, F.
AU - Breyer, M.
AU - Guan, Y.
PY - 2006/5/1
Y1 - 2006/5/1
N2 - Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARα by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n = 8; db/m, n = 6) or a diet containing fenofibrate (db/db, n = 8; db/m, n = 7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P < 0.001) and HbA1c levels (P < 0.001), and was associated with decreased food intake (P < 0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P < 0.001) and reduced plasma insulin levels (P < 0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P < 0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P < 0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARα, decreased type I collagen production. Taken together, the PPARα agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARα by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.
AB - Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARα by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n = 8; db/m, n = 6) or a diet containing fenofibrate (db/db, n = 8; db/m, n = 7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P < 0.001) and HbA1c levels (P < 0.001), and was associated with decreased food intake (P < 0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P < 0.001) and reduced plasma insulin levels (P < 0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P < 0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P < 0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARα, decreased type I collagen production. Taken together, the PPARα agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARα by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.
KW - Diabetic nephropathy
KW - Fenofibrate
KW - PPARα
KW - Type II diabetes
UR - http://www.scopus.com/inward/record.url?scp=33646508121&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646508121&partnerID=8YFLogxK
U2 - 10.1038/sj.ki.5000209
DO - 10.1038/sj.ki.5000209
M3 - Article
C2 - 16672921
AN - SCOPUS:33646508121
VL - 69
SP - 1511
EP - 1517
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 9
ER -