Galantamine improves glycemic control and diabetic nephropathy in Leprdb/db mice

Galantamine, a centrally acting acetylcholinesterase inhibitor, has been shown to attenuate inflammation and insulin resistance in patients with metabolic syndrome. We investigated the effects of galantamine on glycemic control and development of diabetic nephropathy (DN) in Lepr db/db mice. Galanta...

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Bibliographic Details
Published in:Scientific reports 2023-09, Vol.13 (1), p.15544-15544, Article 15544
Main Authors: Meng, Qinghe, Ma, Julia, Suo, Liye, Pruekprasert, Napat, Chakrapani, Prithi, Cooney, Robert N.
Format: Article
Language:English
Subjects:
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Acetylcholinesterase
Apoptosis
Body weight
Caspase-1
Cholinesterase inhibitors
Creatinine
Diabetes
Diabetes mellitus
Diabetic nephropathy
Food
Food intake
Galantamine
Glucose
Histology
Humanities and Social Sciences
Hyperglycemia
Inflammation
Insulin resistance
Kidneys
MAP kinase
Metabolic disorders
Metabolic syndrome
multidisciplinary
Nephropathy
Plasma
Renal function
Science
Science (multidisciplinary)
Tumor necrosis factor-α
Weight control
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Summary:Galantamine, a centrally acting acetylcholinesterase inhibitor, has been shown to attenuate inflammation and insulin resistance in patients with metabolic syndrome. We investigated the effects of galantamine on glycemic control and development of diabetic nephropathy (DN) in Lepr db/db mice. Galantamine significantly reduced food intake, body weight, blood glucose and HbA1c levels. Insulin resistance (HOMA-IR, QUICKI), HOMA-β and elevations in plasma inflammatory cytokine levels (TNF-α, IL-6 and HMGB-1) were all attenuated by galantamine. Galantamine also ameliorated diabetes-induced kidney injury as evidenced by improvements in renal function (BUN, creatinine, albuminuria), histologic injury and apoptosis. Improved glycemic control and nephropathy were associated with increased circulating GLP-1, decreased renal P-38 MAPK and caspase-1 activation and reduced SGLT-2 expression. These findings provide insights into the mechanisms by which galantamine improves glycemic control and attenuates DN in the Lepr db/db mouse model.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-42665-2