PMID- 23092114
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20220310
IS  - 1746-045X (Electronic)
IS  - 1746-0441 (Print)
IS  - 1746-0441 (Linking)
VI  - 8
IP  - 1
DP  - 2013 Jan
TI  - Novel directions for diabetes mellitus drug discovery.
PG  - 35-48
LID - 10.1517/17460441.2013.736485 [doi]
AB  - INTRODUCTION: Diabetes mellitus impacts almost 200 million individuals worldwide 
      and leads to debilitating complications. New avenues of drug discovery must 
      target the underlying cellular processes of oxidative stress, apoptosis, 
      autophagy, and inflammation that can mediate multi-system pathology during 
      diabetes mellitus. AREAS COVERED: The authors examine the novel directions for 
      drug discovery that involve: the beta-nicotinamide adenine dinucleotide (NAD(+)) 
      precursor nicotinamide, the cytokine erythropoietin, the NAD(+)-dependent protein 
      histone deacetylase SIRT1, the serine/threonine-protein kinase mammalian target 
      of rapamycin (mTOR), and the wingless pathway. Furthermore, the authors present 
      the implications for the targeting of these pathways that oversee gluconeogenic 
      genes, insulin signaling and resistance, fatty acid beta-oxidation, inflammation, 
      and cellular survival. EXPERT OPINION: Nicotinamide, erythropoietin, and the 
      downstream pathways of SIRT1, mTOR, forkhead transcription factors, and wingless 
      signaling offer exciting prospects for novel directions of drug discovery for the 
      treatment of metabolic disorders. Future investigations must dissect the complex 
      relationship and fine modulation of these pathways for the successful translation 
      of robust reparative and regenerative strategies against diabetes mellitus and 
      the complications of this disorder.
FAU - Maiese, Kenneth
AU  - Maiese K
AD  - New Jersey Health Sciences University, Cancer Institute of New Jersey, Laboratory 
      of Cellular and Molecular Signaling , Newark, NJ 07101, USA. wntin75@yahoo.com
FAU - Chong, Zhao Zhong
AU  - Chong ZZ
FAU - Shang, Yan Chen
AU  - Shang YC
FAU - Wang, Shaohui
AU  - Wang S
LA  - eng
GR  - R01 NS053946/NS/NINDS NIH HHS/United States
GR  - NS059346-03S1/NS/NINDS NIH HHS/United States
GR  - NS059346-04/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20121024
PL  - England
TA  - Expert Opin Drug Discov
JT  - Expert opinion on drug discovery
JID - 101295755
RN  - 0 (Hypoglycemic Agents)
RN  - 11096-26-7 (Erythropoietin)
RN  - 25X51I8RD4 (Niacinamide)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus/*drug therapy/*metabolism
MH  - Drug Delivery Systems/methods/trends
MH  - Drug Discovery/*methods/*trends
MH  - Erythropoietin/administration & dosage/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/metabolism
MH  - Niacinamide/administration & dosage/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3529804
MID - NIHMS416484
EDAT- 2012/10/25 06:00
MHDA- 2013/10/18 06:00
PMCR- 2014/01/01
CRDT- 2012/10/25 06:00
PHST- 2012/10/25 06:00 [entrez]
PHST- 2012/10/25 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.1517/17460441.2013.736485 [doi]
PST - ppublish
SO  - Expert Opin Drug Discov. 2013 Jan;8(1):35-48. doi: 10.1517/17460441.2013.736485. 
      Epub 2012 Oct 24.