Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice.
Animals
Benzhydryl Compounds
/ pharmacology
Blood Glucose
/ drug effects
Diabetes Mellitus, Type 2
/ drug therapy
Dipeptidyl-Peptidase IV Inhibitors
/ pharmacology
Disease Models, Animal
Drug Combinations
Glucosides
/ pharmacology
Hypoglycemic Agents
/ pharmacology
Insulin
/ metabolism
Insulin-Secreting Cells
/ drug effects
Linagliptin
/ pharmacology
Male
Mice
Mice, Inbred NOD
/ metabolism
Mice, Inbred Strains
Sodium-Glucose Transporter 2
/ metabolism
Sodium-Glucose Transporter 2 Inhibitors
/ pharmacology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 08 2021
09 08 2021
Historique:
received:
10
12
2020
accepted:
19
07
2021
entrez:
10
8
2021
pubmed:
11
8
2021
medline:
16
11
2021
Statut:
epublish
Résumé
Effects of combination therapy of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor on β-cells are still unclear, although combination agent of these two drugs has become common in clinical practice. Therefore, we aimed to elucidate the effects of DPP-4 inhibitor and/or SGLT2 inhibitor on β-cell mass and function and compared their effects between in an early and advanced phase of diabetes. We used 7-week-old db/db mice as an early phase and 16-week-old mice as an advanced phase and treated them for 2 weeks with oral administration of linagliptin, empagliflozin, linagliptin + empagliflozin (L + E group), and 0.5% carboxymethylcellulose (Cont group). Blood glucose levels in Empa and L + E group were significantly lower than Cont group after treatment. In addition, β-cell mass in L + E group was significantly larger than Cont group only in an early phase, accompanied by increased Ki67-positive β-cell ratio. In isolated islets, mRNA expression levels of insulin and its transcription factors were all significantly higher only in L + E group in an early phase. Furthermore, mRNA expression levels related to β-cell differentiation and proliferation were significantly increased only in L + E group in an early phase. In conclusion, combination of DPP-4 inhibitor and SGLT2 inhibitor exerts more beneficial effects on β-cell mass and function, especially in an early phase of diabetes rather than an advanced phase.
Identifiants
pubmed: 34373487
doi: 10.1038/s41598-021-94896-w
pii: 10.1038/s41598-021-94896-w
pmc: PMC8352868
doi:
Substances chimiques
Benzhydryl Compounds
0
Blood Glucose
0
Dipeptidyl-Peptidase IV Inhibitors
0
Drug Combinations
0
Glucosides
0
Hypoglycemic Agents
0
Insulin
0
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
Linagliptin
3X29ZEJ4R2
empagliflozin
HDC1R2M35U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16120Informations de copyright
© 2021. The Author(s).
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