PMID- 37985011
OWN - NLM
STAT- MEDLINE
DCOM- 20240118
LR  - 20240118
IS  - 1365-2826 (Electronic)
IS  - 0953-8194 (Linking)
VI  - 36
IP  - 1
DP  - 2024 Jan
TI  - Alzheimer's disease-related brain insulin resistance and the prospective 
      therapeutic impact of metformin.
PG  - e13356
LID - 10.1111/jne.13356 [doi]
AB  - Besides COVID-19, two of the most critical outbreaks of our day are insulin 
      resistance, type 2 diabetes mellitus (T2DM), and Alzheimer's disease (AD). Each 
      disease's pathophysiology is well established. Furthermore, a substantial overlap 
      between them has coexisted. Uncertainty remains on whether T2DM and AD are 
      parallel illnesses with the same origin or separate illnesses linked through 
      violent pathways. The current study was aimed at testing whether the insulin 
      resistance in the brain results in AD symptoms or not. Insulin resistance was 
      induced in the brains of rats using a single intracerebroventricular 
      streptozotocin (STZ) dose. We then measured glucose, insulin receptor substrate 2 
      (IRS-2), amyloid beta (Abeta) deposition, and tau phosphorylation in the brain to look 
      for signs of insulin resistance and AD. The results of this study indicated that 
      a single dose of STZ was able to induce insulin resistance in the brain and 
      significantly decline IRS-2. This resistance was accompanied by obvious memory 
      loss, Abeta deposition, and tau phosphorylation, further visible diminishing in 
      neurotransmitters such as dopamine and acetylcholine. Furthermore, oxidative 
      stress was increased due to the antioxidant system being compromised. 
      Interestingly, the pancreas injury and peripheral insulin resistance coexisted 
      with brain insulin resistance. Indeed, the antidiabetic metformin was able to 
      enhance all these drastic effects. In conclusion, brain insulin resistance could 
      lead to AD and vice versa. These are highly linked syndromes that could influence 
      peripheral organs. Further studies are required to stabilize this putative 
      pathobiology relationship between them.
CI  - (c) 2023 British Society for Neuroendocrinology.
FAU - Abosharaf, Hamed A
AU  - Abosharaf HA
AUID- ORCID: 0000-0003-3850-4258
AD  - Biochemistry Division, Chemistry Department, Faculty of Science, Tanta 
      University, Tanta, Egypt.
FAU - Elsonbaty, Yasmin
AU  - Elsonbaty Y
AD  - Biochemistry Division, Chemistry Department, Faculty of Science, Tanta 
      University, Tanta, Egypt.
FAU - Tousson, Ehab
AU  - Tousson E
AD  - Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.
FAU - M Mohamed, Tarek
AU  - M Mohamed T
AD  - Biochemistry Division, Chemistry Department, Faculty of Science, Tanta 
      University, Tanta, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20231120
PL  - United States
TA  - J Neuroendocrinol
JT  - Journal of neuroendocrinology
JID - 8913461
RN  - 0 (Amyloid beta-Peptides)
RN  - 9100L32L2N (Metformin)
RN  - 0 (Insulin)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Alzheimer Disease/metabolism
MH  - *Insulin Resistance/physiology
MH  - Amyloid beta-Peptides/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - *Metformin/pharmacology/metabolism
MH  - Insulin/metabolism
MH  - Brain/metabolism
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Alzheimer disease
OT  - amyloid beta
OT  - brain insulin resistance
OT  - insulin receptor substrate 2
OT  - metformin
EDAT- 2023/11/21 01:07
MHDA- 2024/01/18 06:43
CRDT- 2023/11/20 20:53
PHST- 2023/06/11 00:00 [revised]
PHST- 2023/02/28 00:00 [received]
PHST- 2023/10/08 00:00 [accepted]
PHST- 2024/01/18 06:43 [medline]
PHST- 2023/11/21 01:07 [pubmed]
PHST- 2023/11/20 20:53 [entrez]
AID - 10.1111/jne.13356 [doi]
PST - ppublish
SO  - J Neuroendocrinol. 2024 Jan;36(1):e13356. doi: 10.1111/jne.13356. Epub 2023 Nov 
      20.