PMID- 35017046
OWN - NLM
STAT- MEDLINE
DCOM- 20220321
LR  - 20220321
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 176
DP  - 2022 Feb
TI  - Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors 
      treatment.
PG  - 106062
LID - S1043-6618(22)00007-X [pii]
LID - 10.1016/j.phrs.2022.106062 [doi]
AB  - Gliflozins are a novel class of oral anti-diabetic drugs, acting as inhibitors of 
      sodium-glucose co-transporters (SGLTs) through the proximal convoluted tubules 
      (PCT) and intestinal epithelium. The sodium-glucose co-transporters 2 (SGLT2) are 
      mainly expressed in S1 and S2 segments of the proximal convoluted tubule in the 
      kidneys. Clinical guidelines recommend their use especially in Type 2 Diabetes 
      mellitus (T2DM) patients with vascular complications and/or heart failure 
      highlighting the importance of sodium-glucose co-transporter 2 inhibitors 
      (SGLT2i) pleiotropic effects. Interestingly, cognitive decline is a widely 
      recognized complication of T2DM and, in addition, to clarify its pathophysiology, 
      there is an urgent need to understand how and if diabetes therapies can control 
      diabetes-related cognitive dysfunction. At the time, although SGLT2 proteins are 
      present in the Central Nervous System (CNS), the SGLT2i effects on cognitive 
      impairments remain partly unknown. In pre-clinical studies, SGLT2i ameliorates 
      cognitive dysfunction in obese and T2DM mice, reducing oxidative stress, 
      neuroinflammation and improving neuronal plasticity and mitochondrial brain 
      pathway. In addition, SGLT2i could bring back mTOR to a physiological state of 
      activation, stopping neurodegenerative diseases' onset or progression. Instead, 
      clinical studies on T2DM-related cognitive dysfunction treated by SGLT2i are much 
      more limited. For these reasons, further studies are needed to better elucidate 
      if SGLT2i therapy can affect T2DM-related cognitive decline. In this scenario, 
      this review aims to summarize the state of knowledge on the role of SGLT2i in 
      T2DM-related cognitive dysfunction and stimulate new clinical trials.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Rizzo, Maria Rosaria
AU  - Rizzo MR
AD  - Department of Advanced Medical and Surgical Sciences - University of Campania 
      "Luigi Vanvitelli", 80138 Naples, Italy. Electronic address: 
      mariarosaria.rizzo@unicampania.it.
FAU - Di Meo, Irene
AU  - Di Meo I
AD  - Department of Advanced Medical and Surgical Sciences - University of Campania 
      "Luigi Vanvitelli", 80138 Naples, Italy.
FAU - Polito, Rita
AU  - Polito R
AD  - Department of Advanced Medical and Surgical Sciences - University of Campania 
      "Luigi Vanvitelli", 80138 Naples, Italy.
FAU - Auriemma, Maria Chiara
AU  - Auriemma MC
AD  - Department of Advanced Medical and Surgical Sciences - University of Campania 
      "Luigi Vanvitelli", 80138 Naples, Italy.
FAU - Gambardella, Antonio
AU  - Gambardella A
AD  - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 
      80138 Naples, Italy.
FAU - di Mauro, Gabriella
AU  - di Mauro G
AD  - Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", 
      University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
FAU - Capuano, Annalisa
AU  - Capuano A
AD  - Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", 
      University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
FAU - Paolisso, Giuseppe
AU  - Paolisso G
AD  - Department of Advanced Medical and Surgical Sciences - University of Campania 
      "Luigi Vanvitelli", 80138 Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220110
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Cognitive Dysfunction/*drug therapy/etiology
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy
MH  - Humans
MH  - Neuroprotective Agents/*therapeutic use
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use
OTO - NOTNLM
OT  - Central Nervous System (CNS)
OT  - Cognitive impairment
OT  - Gliflozins
OT  - SGLT2 inhibitors
OT  - Sodium-glucose co-transporter (SGLT)
OT  - Type 2 diabetes mellitus (T2DM)
EDAT- 2022/01/13 06:00
MHDA- 2022/03/22 06:00
CRDT- 2022/01/12 05:53
PHST- 2021/11/24 00:00 [received]
PHST- 2022/01/03 00:00 [revised]
PHST- 2022/01/04 00:00 [accepted]
PHST- 2022/01/13 06:00 [pubmed]
PHST- 2022/03/22 06:00 [medline]
PHST- 2022/01/12 05:53 [entrez]
AID - S1043-6618(22)00007-X [pii]
AID - 10.1016/j.phrs.2022.106062 [doi]
PST - ppublish
SO  - Pharmacol Res. 2022 Feb;176:106062. doi: 10.1016/j.phrs.2022.106062. Epub 2022 
      Jan 10.