PMID- 37078106
OWN - NLM
STAT- MEDLINE
DCOM- 20230512
LR  - 20230513
IS  - 1753-0407 (Electronic)
IS  - 1753-0393 (Print)
IS  - 1753-0407 (Linking)
VI  - 15
IP  - 5
DP  - 2023 May
TI  - Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: 
      Controversial points and a promising arena.
PG  - 397-408
LID - 10.1111/1753-0407.13389 [doi]
AB  - Neprilysin (NEP) is a transmembrane zinc-dependent metalloproteinase that 
      inactivates various peptide hormones including glucagon-like peptide 1 (GLP-1). 
      NEP inhibitors may be effective in the management of type 2 diabetes mellitus 
      (T2DM) by increasing the circulating level of GLP-1. However, acute-effect NEP 
      inhibitors may lead to detrimental effects by increasing blood glucose 
      independent of GLP-1. These findings suggest a controversial point regarding the 
      potential role of NEP inhibitors on glucose homeostasis in T2DM patients. 
      Therefore, this perspective aimed to clarify the controversial points concerning 
      the role of NEP inhibitors on glucose homeostasis in T2DM. NEP inhibitors may 
      lead to beneficial effects by inhibition of NEP, which is involved in the 
      impairment of glucose homeostasis through modulation of insulin resistance. NEP 
      increases dipeptidyl peptidase-4 (DPP4) activity and contributes to increasing 
      active GLP-1 proteolysis so NEP inhibitors may improve glycemic control through 
      increasing endogenous GLP-1 activity and reduction of DPP4 activity. Thus, NEP 
      inhibitors could be effective alone or in combination with antidiabetic agents in 
      treating T2DM patients. However, long-term and short-term effects of NEP 
      inhibitors may lead to a detrimental effect on insulin sensitivity and glucose 
      homeostasis through different mechanisms including augmentation of substrates and 
      pancreatic amyloid deposition. These findings are confirmed in animal but not in 
      humans. In conclusion, NEP inhibitors produce beneficial rather than detrimental 
      effects on glucose homeostasis and insulin sensitivity in humans though most of 
      the detrimental effects of NEP inhibitors are confirmed in animal studies.
CI  - (c) 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai 
      Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
FAU - AlAnazi, Faisal Holil
AU  - AlAnazi FH
AD  - Department of Medicine, College of Medicine, Majmaah University, Majmaah, Saudi 
      Arabia.
FAU - Al-Kuraishy, Hayder M
AU  - Al-Kuraishy HM
AD  - Department of Clinical Pharmacology and Medicine, College of Medicine, 
      ALmustansiriyia University, Baghdad, Iraq.
FAU - Al-Gareeb, Ali I
AU  - Al-Gareeb AI
AD  - Department of Clinical Pharmacology and Medicine, College of Medicine, 
      ALmustansiriyia University, Baghdad, Iraq.
FAU - Alexiou, Athanasios
AU  - Alexiou A
AD  - Department of Science and Engineering, Novel Global Community Educational 
      Foundation, Hebersham, New South Wales, Australia.
AD  - AFNP Med, Wien, Austria.
FAU - Papadakis, Marios
AU  - Papadakis M
AD  - Department of Surgery II, University Hospital Witten-Herdecke, University of 
      Witten-Herdecke, Wuppertal, Germany.
FAU - Ogaly, Hanan A
AU  - Ogaly HA
AUID- ORCID: 0000-0002-0480-5127
AD  - Chemistry Department, College of Science, King Khalid University, Abha, Saudi 
      Arabia.
FAU - Alanazi, Yousef Abud
AU  - Alanazi YA
AUID- ORCID: 0000-0003-1254-0541
AD  - Department of Pediatrics, College of Medicine, Majmaah University, Majmaah, Saudi 
      Arabia.
FAU - Saad, Hebatallah M
AU  - Saad HM
AUID- ORCID: 0000-0001-9555-7300
AD  - Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, 
      Marsa Matruh, Egypt.
FAU - Batiha, Gaber El-Saber
AU  - Batiha GE
AD  - Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, 
      Damanhour University, Damanhour, Egypt.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230419
PL  - Australia
TA  - J Diabetes
JT  - Journal of diabetes
JID - 101504326
RN  - EC 3.4.24.11 (Neprilysin)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Blood Glucose)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Neprilysin
MH  - *Insulin Resistance
MH  - Dipeptidyl Peptidase 4
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Blood Glucose
MH  - Glucagon-Like Peptide 1
MH  - Homeostasis
MH  - *Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use
PMC - PMC10172023
OTO - NOTNLM
OT  - 2型糖尿病
OT  - neprilysin
OT  - sacubitril
OT  - type 2 diabetes mellitus
OT  - 脑啡肽酶
OT  - 脑啡肽酶抑制剂
EDAT- 2023/04/20 06:42
MHDA- 2023/05/12 07:06
PMCR- 2023/04/19
CRDT- 2023/04/20 02:39
PHST- 2023/03/01 00:00 [revised]
PHST- 2022/12/15 00:00 [received]
PHST- 2023/04/02 00:00 [accepted]
PHST- 2023/05/12 07:06 [medline]
PHST- 2023/04/20 06:42 [pubmed]
PHST- 2023/04/20 02:39 [entrez]
PHST- 2023/04/19 00:00 [pmc-release]
AID - JDB13389 [pii]
AID - 10.1111/1753-0407.13389 [doi]
PST - ppublish
SO  - J Diabetes. 2023 May;15(5):397-408. doi: 10.1111/1753-0407.13389. Epub 2023 Apr 
      19.