PMID- 28767672
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 8
DP  - 2017
TI  - Bi-stability in type 2 diabetes mellitus multi-organ signalling network.
PG  - e0181536
LID - 10.1371/journal.pone.0181536 [doi]
LID - e0181536
AB  - Type 2 diabetes mellitus (T2DM) is believed to be irreversible although no 
      component of the pathophysiology is irreversible. We show here with a network 
      model that the apparent irreversibility is contributed by the structure of the 
      network of inter-organ signalling. A network model comprising all known 
      inter-organ signals in T2DM showed bi-stability with one insulin sensitive and 
      one insulin resistant attractor. The bi-stability was made robust by multiple 
      positive feedback loops suggesting an evolved allostatic system rather than a 
      homeostatic system. In the absence of the complete network, impaired insulin 
      signalling alone failed to give a stable insulin resistant or hyperglycemic 
      state. The model made a number of correlational predictions many of which were 
      validated by empirical data. The current treatment practice targeting obesity, 
      insulin resistance, beta cell function and normalization of plasma glucose failed 
      to reverse T2DM in the model. However certain behavioural and neuro-endocrine 
      interventions ensured a reversal. These results suggest novel prevention and 
      treatment approaches which need to be tested empirically.
FAU - Kulkarni, Shubhankar
AU  - Kulkarni S
AD  - Biology, Indian Institute of Science Education and Research, Pashan, Pune, 
      Maharashtra, India.
FAU - Sharda, Sakshi
AU  - Sharda S
AD  - Institute of Ecology and Evolution, University of Bern, Bern, Switzerland.
FAU - Watve, Milind
AU  - Watve M
AUID- ORCID: 0000-0003-0730-8393
AD  - Biology, Indian Institute of Science Education and Research, Pashan, Pune, 
      Maharashtra, India.
LA  - eng
PT  - Journal Article
DEP - 20170802
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Insulin)
SB  - IM
MH  - Diabetes Mellitus, Type 2/blood/*metabolism
MH  - Feedback, Physiological
MH  - Glucose Intolerance/blood/*metabolism
MH  - Humans
MH  - Insulin/*blood
MH  - Insulin Resistance
MH  - Models, Biological
MH  - Signal Transduction
PMC - PMC5540287
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/08/03 06:00
MHDA- 2017/10/03 06:00
PMCR- 2017/08/02
CRDT- 2017/08/03 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2017/07/03 00:00 [accepted]
PHST- 2017/08/03 06:00 [entrez]
PHST- 2017/08/03 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2017/08/02 00:00 [pmc-release]
AID - PONE-D-16-48371 [pii]
AID - 10.1371/journal.pone.0181536 [doi]
PST - epublish
SO  - PLoS One. 2017 Aug 2;12(8):e0181536. doi: 10.1371/journal.pone.0181536. 
      eCollection 2017.