PMID- 19651294
OWN - NLM
STAT- MEDLINE
DCOM- 20100108
LR  - 20211203
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 41
IP  - 6 Suppl
DP  - 2009 Jul-Aug
TI  - Mammalian target of rapamycin and diabetes: what does the current evidence tell 
      us?
PG  - S31-8
LID - 10.1016/j.transproceed.2009.06.159 [doi]
AB  - New-onset diabetes mellitus after transplantation (NODAT) is a serious 
      complication in organ transplantation; not only does it enhance the risk of graft 
      dysfunction, it also increases cardiovascular morbidity and mortality. The 
      mammalian target of rapamycin (mTOR) is regulated independently by insulin, amino 
      acids, and energy sufficiency. It integrates signal from growth factors, 
      hormones, nutrients, and cellular energy levels to regulate protein translation 
      and cell growth, proliferation, and survival. In addition, mTOR generates an 
      inhibitory feedback loop on insulin receptor substrate (IRS) proteins. Therefore, 
      it was suggested that mTOR might link nutrient excess with both obesity and 
      insulin resistance. In this review, we summarize the role of mTOR and its 
      inhibitor sirolimus (SRL) on chronic hyperglycemia and insulin resistance in beta 
      cells, adipose tissue, liver, and muscle. We further hypothesize, based on data 
      from the literature and generated in our laboratory, that SRL could counteract 
      the development of NODAT in stable glucose homeostasis due to its positive 
      effects on insulin-stimulated glucose uptake, whereas in conditions that require 
      an adaptive beta cell proliferation (such as pregnancy and weight increase), the 
      administration of SRL might have effects that would promote the development of 
      NODAT. Therefore, it seems crucial for patient outcome to consider these 
      potentially contrasting effects of SRL.
FAU - Vodenik, B
AU  - Vodenik B
AD  - Department of Nephrology and Renal Transplantation, Laboratori Experimental de 
      Nefrologia I Trasplantament (LENIT), Hospital Clinic i Provincial de Barcelona, 
      Barcelona, Spain.
FAU - Rovira, J
AU  - Rovira J
FAU - Campistol, J M
AU  - Campistol JM
LA  - eng
PT  - Journal Article
DEP - 20090719
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Amino Acids)
RN  - 0 (CRTC2 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acids/pharmacology
MH  - Cell Division
MH  - Cell Survival
MH  - Diabetes Mellitus/*epidemiology/mortality
MH  - Energy Metabolism
MH  - Female
MH  - Humans
MH  - Insulin/pharmacology
MH  - Insulin-Secreting Cells/physiology
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes
MH  - Obesity/epidemiology
MH  - Organ Transplantation/*adverse effects
MH  - Postoperative Complications/epidemiology/mortality
MH  - Pregnancy
MH  - Pregnancy Complications/epidemiology
MH  - Protein Kinases/drug effects/physiology
MH  - Proteins
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/physiology
EDAT- 2009/08/11 09:00
MHDA- 2010/01/09 06:00
CRDT- 2009/08/05 09:00
PHST- 2009/08/05 09:00 [entrez]
PHST- 2009/08/11 09:00 [pubmed]
PHST- 2010/01/09 06:00 [medline]
AID - S0041-1345(09)00894-X [pii]
AID - 10.1016/j.transproceed.2009.06.159 [doi]
PST - ppublish
SO  - Transplant Proc. 2009 Jul-Aug;41(6 Suppl):S31-8. doi: 
      10.1016/j.transproceed.2009.06.159. Epub 2009 Jul 19.