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Dipeptidyl Peptidase 4, a Novel Adipokine, Impairs Retinal Microcirculation in Patients With Type 2 Diabetes Mellitus
Tsuneaki Omae1, Shinji Ono1, Takayuki Kamiya1
1Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
Purpose:
The study objective was to examine the role of dipeptidyl peptidase 4 (DPP4) on retinal microcirculation in patients with type 2 diabetes mellitus (DM) and an in vitro study.
Methods:
Sixty-seven patients with type 2 diabetes and minimal diabetic retinopathy (DR) were divided into two groups based on gender. We compared the patients' retinal circulatory parameters measured with laser Doppler velocimetry and serum DPP4 concentrations. Using isolated retinal arterioles, we also compared the retinal endothelial function before and after DPP4 incubation.
Results:
The plasma DPP4 concentrations were correlated negatively with the retinal vessel diameter (D) and retinal blood flow (RBF) in men but not women. Multiple regression analysis showed that the plasma DPP4 level was independently and negatively correlated with the vessel D. In vitro, intraluminal DPP4 treatment significantly attenuated endothelium-dependent nitric oxide (NO)-mediated vasodilation with a dose-dependent manner. Superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the NADPH oxidase inhibitor apocynin, and the DPP4 inhibitor teneligliptin, prevented the retinal endothelial dysfunction induced by DPP4.
Conclusions:
Our results indicated that high serum DPP4 concentration may be associated with decreased RBF, probably via the constricted vessel D in men with type 2 diabetes with early-phase DR and further that DPP4 may inhibit endothelium-dependent NO-mediated dilation in the retinal arterioles via producing superoxide from NADPH oxidase.
Insights
High dipeptidyl peptidase 4 (DPP4) levels are linked to reduced retinal blood flow in men with type 2 diabetes and early diabetic retinopathy. DPP4 impairs blood vessel dilation by increasing oxidative stress.
Area of Science:
- Ophthalmology
- Endocrinology
- Cardiovascular Research
Background:
- Type 2 diabetes mellitus (DM) is a leading cause of diabetic retinopathy (DR).
- Diabetic retinopathy affects retinal microcirculation, potentially impacting blood flow and vessel function.
- Dipeptidyl peptidase 4 (DPP4) is an enzyme increasingly recognized for its systemic effects, including potential roles in microvascular complications.
Purpose of the Study:
- To investigate the association between serum dipeptidyl peptidase 4 (DPP4) concentrations and retinal microcirculation in patients with type 2 DM and minimal DR.
- To explore the in vitro effects of DPP4 on retinal arteriolar endothelial function.
Main Methods:
- Sixty-seven patients with type 2 DM and minimal DR were stratified by gender.
- Retinal circulatory parameters (vessel diameter, blood flow) were measured using laser Doppler velocimetry.
- Isolated retinal arterioles were used to assess endothelial function before and after DPP4 incubation.
Main Results:
- Serum DPP4 concentrations negatively correlated with retinal vessel diameter and blood flow in men, but not women.
- In vitro, DPP4 significantly reduced nitric oxide (NO)-mediated vasodilation in a dose-dependent manner.
- DPP4-induced endothelial dysfunction was mitigated by superoxide scavengers, NADPH oxidase inhibitors, and a DPP4 inhibitor.
Conclusions:
- Elevated serum DPP4 may contribute to reduced retinal blood flow in men with type 2 DM and early DR, likely due to vessel constriction.
- DPP4 appears to impair endothelium-dependent vasodilation in retinal arterioles by promoting superoxide production via NADPH oxidase.
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