PMID- 37238649
OWN - NLM
STAT- MEDLINE
DCOM- 20230529
LR  - 20230531
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 13
IP  - 5
DP  - 2023 Apr 30
TI  - Molecular Mechanisms of Obesity-Induced Development of Insulin Resistance and 
      Promotion of Amyloid-beta Accumulation: Dietary Therapy Using Weak Organic Acids via 
      Improvement of Lowered Interstitial Fluid pH.
LID - 10.3390/biom13050779 [doi]
LID - 779
AB  - Insulin resistance is one of the etiologies of type 2 diabetes mellitus (T2DM) 
      and has been suggested to contribute to the development of Alzheimer's disease by 
      promoting amyloid-beta accumulation. Various causes of insulin resistance have been 
      suggested; however, mechanisms of insulin resistance development remain to be 
      elucidated in many respects. Elucidating the mechanisms underlying the 
      development of insulin resistance is one of the key factors in developing methods 
      to prevent the onset of T2DM and Alzheimer's disease. It has been suggested that 
      the body pH environment plays an important role in the control of cellular 
      functions by regulating the action of hormones including insulin and the activity 
      of enzymes and neurons, thereby maintaining homeostatic conditions of the body. 
      This review introduces: (1) Mitochondrial dysfunction through oxidative stress 
      caused by obesity-induced inflammation. (2) Decreased pH of interstitial fluid 
      due to mitochondrial dysfunction. (3) Development of insulin resistance due to 
      diminution of insulin affinity to its receptor caused by the lowered interstitial 
      fluid pH. (4) Accelerated accumulation of amyloid-beta due to elevated activities of 
      beta- and gamma-secretases caused by the lowered interstitial fluid pH. (5) Diet 
      therapies for improving insulin resistance with weak organic acids that act as 
      bases in the body to raise the pH of lowered interstitial fluid and food factors 
      that promote absorption of weak organic acids in the gut.
FAU - Marunaka, Yoshinori
AU  - Marunaka Y
AUID- ORCID: 0000-0003-3846-0937
AD  - Medical Research Institute, Kyoto Industrial Health Association, Kyoto 604-8472, 
      Japan.
AD  - Research Organization of Science and Technology, Ritsumeikan University, Kusatsu 
      525-8577, Japan.
AD  - Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 
      Kyoto 602-8566, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230430
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Insulin)
RN  - 0 (Organic Chemicals)
SB  - IM
MH  - Humans
MH  - *Insulin Resistance/physiology
MH  - *Alzheimer Disease/etiology
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Extracellular Fluid
MH  - Amyloid beta-Peptides
MH  - Insulin
MH  - Obesity/drug therapy/etiology
MH  - Organic Chemicals
MH  - Hydrogen-Ion Concentration
PMC - PMC10216820
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - SMCT1
OT  - acidosis
OT  - amyloid-beta
OT  - insulin resistance
OT  - interstitial fluid pH
OT  - ketone bodies
OT  - pH capacity
OT  - type 2 diabetes mellitus
OT  - weak organic acids
COIS- The author declares no conflict of interest.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/29 06:41
PMCR- 2023/04/30
CRDT- 2023/05/27 01:07
PHST- 2023/02/04 00:00 [received]
PHST- 2023/03/31 00:00 [revised]
PHST- 2023/04/28 00:00 [accepted]
PHST- 2023/05/29 06:41 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:07 [entrez]
PHST- 2023/04/30 00:00 [pmc-release]
AID - biom13050779 [pii]
AID - biomolecules-13-00779 [pii]
AID - 10.3390/biom13050779 [doi]
PST - epublish
SO  - Biomolecules. 2023 Apr 30;13(5):779. doi: 10.3390/biom13050779.