Sarpogrelate hydrochloride, a serotonin2A receptor antagonist, reduces albuminuria in diabetic patients with early-stage diabetic nephropathy
Abstract
We have recently demonstrated that serotonin (5-HT) increases the production of type 4 collagen by cultured human mesangial cells. Here we examined the clinical effects of a 5-HT(A2) receptor antagonist whether it would prevent the development or progression of diabetic nephropathy. We compared the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the major metabolite of 5-HT, in 24-h urine samples of patients with type 2 diabetes (n=110) and normal subjects (n=40). We then investigated the effects of 24-month treatment with sarpogrelate hydrochloride, a 5-HT(A2) receptor antagonist, on urinary albumin level in 10 type 2 diabetics with microalbuminuria, compared with not treated control group. Urinary 5-HIAA in diabetic patients was significantly higher (3.44+/-1.43 mg/day) than in normal subjects (1.62+/-0.50 mg/day, P<0.001), and correlated significantly with hemoglobin A1c (r=0.56, P<0.001) and with fasting blood glucose (r=0.37, P<0.001). Sarpogrelate significantly reduced urinary albumin excretion level within 3 months of commencement of treatment (24.3+/-8.58 mg/g Cr, P<0.05), which was persistently seen during the treatment, while no such change was noted in the control group (32.2+/-13.4 mg/g Cr). Our study indicate that high levels of 5-HT in type 2 diabetics may be one of the underlying mechanisms of diabetic nephropathy, and that treatment with 5-HT(A2) receptor antagonists may reduce or inhibit the development of nephropathy.
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Gut-derived 5-HT can modulate glucose and energy homeostasis and is augmented in patients with type 2 diabetes and the obese.
“Furthermore, gut-derived 5-HT can also modulate glucose and energy homeostasis (68-70), and is augmented in patients with type 2 diabetes (71) and the obese (9).”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [71]
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- Authors
- Takahashi, T., Yano, M., Minami, J., Haraguchi, T., Koga, N., Higashi, K., & Kobori, S.
- Affiliations
- Kumamoto Medical Center (JP)
- Corresponding author
- Takahashi, Takeshi
- ORCID
- Takahashi, Takeshi
- Venue
- Diabetes Research and Clinical Practice
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 58
- Issue
- 2
- Pages
- 123-129
- ISSN
- 0168-8227 (ISSN-L)
- OpenAlex
- W2088914402
- Cited by
- 72
- References
- 15
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 1 · 2012: 3
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Research and Clinical Practice (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- sarpogrelate hydrochloride, diabetic nephropathy, albuminuria, microalbuminuria, type 2 diabetes, serotonin, mesangial cells, type IV collagen, HbA1c
- MeSH terms
- Albuminuria, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Male, Middle Aged, Receptors, Serotonin, Reference Values, Regression Analysis, Serotonin, Serotonin Antagonists, Succinates, Time Factors, Receptor, Serotonin, 5-HT2A
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