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Chaperonin-containing t-complex protein-1 subunit β as a possible biomarker for the phase of glomerular hyperfiltration of diabetic nephropathy.

Wu CZ, Chang LC, Lin YF, Hung YJ, Pei D, Chen JS - Dis. Markers (2015)

Bottom Line: Results showed that C cr and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model.By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients.Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunit β (TCP-1β) and early diabetic nephropathy (DN). In this study, we further explored the relationships between TCP-1β and type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (C cr), and kidney tissues were harvested for evaluation of TCP-1β expression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1β. Results showed that C cr and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1β was expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.

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Related in: MedlinePlus

Change of insulin resistance (HOMA-IR) and creatinine clearance (Ccr) in control (C), high-fat diet (HF), and type 2 diabetes mellitus (DM) mice groups. (a) The HOMA-IR levels in HF and DM groups were significantly higher than those in C group on week 1 and week 4 after induction. (b) The change of murine CCr in the DM group was significantly higher than in C group on week 4. ∗P < 0.05.
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fig1: Change of insulin resistance (HOMA-IR) and creatinine clearance (Ccr) in control (C), high-fat diet (HF), and type 2 diabetes mellitus (DM) mice groups. (a) The HOMA-IR levels in HF and DM groups were significantly higher than those in C group on week 1 and week 4 after induction. (b) The change of murine CCr in the DM group was significantly higher than in C group on week 4. ∗P < 0.05.

Mentions: Insulin resistance (HOMA-IR) is the hallmark of type 2 DM. Figure 1(a) shows HOMA-IR gradually elevated in both HF and DM groups, suggesting that the typical characteristic of type 2 DM was successfully developed in our type 2 DM mice model. Compared to control and HF groups, the DM group developed insulin resistance sooner and a more prominent HOMA-IR elevation was obtained. Meanwhile, hyperglycemia, the fundamental characteristic of type 2 DM, is a defining criterion to judge the success of DM models. Together, hyperglycemia and insulin resistance, the two important clinical features of type 2 DM, could both be noted in our type 2 DM mice model.


Chaperonin-containing t-complex protein-1 subunit β as a possible biomarker for the phase of glomerular hyperfiltration of diabetic nephropathy.

Wu CZ, Chang LC, Lin YF, Hung YJ, Pei D, Chen JS - Dis. Markers (2015)

Change of insulin resistance (HOMA-IR) and creatinine clearance (Ccr) in control (C), high-fat diet (HF), and type 2 diabetes mellitus (DM) mice groups. (a) The HOMA-IR levels in HF and DM groups were significantly higher than those in C group on week 1 and week 4 after induction. (b) The change of murine CCr in the DM group was significantly higher than in C group on week 4. ∗P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402165&req=5

fig1: Change of insulin resistance (HOMA-IR) and creatinine clearance (Ccr) in control (C), high-fat diet (HF), and type 2 diabetes mellitus (DM) mice groups. (a) The HOMA-IR levels in HF and DM groups were significantly higher than those in C group on week 1 and week 4 after induction. (b) The change of murine CCr in the DM group was significantly higher than in C group on week 4. ∗P < 0.05.
Mentions: Insulin resistance (HOMA-IR) is the hallmark of type 2 DM. Figure 1(a) shows HOMA-IR gradually elevated in both HF and DM groups, suggesting that the typical characteristic of type 2 DM was successfully developed in our type 2 DM mice model. Compared to control and HF groups, the DM group developed insulin resistance sooner and a more prominent HOMA-IR elevation was obtained. Meanwhile, hyperglycemia, the fundamental characteristic of type 2 DM, is a defining criterion to judge the success of DM models. Together, hyperglycemia and insulin resistance, the two important clinical features of type 2 DM, could both be noted in our type 2 DM mice model.

Bottom Line: Results showed that C cr and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model.By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients.Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunit β (TCP-1β) and early diabetic nephropathy (DN). In this study, we further explored the relationships between TCP-1β and type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (C cr), and kidney tissues were harvested for evaluation of TCP-1β expression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1β. Results showed that C cr and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1β was expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.

Show MeSH
Related in: MedlinePlus