PMID- 25070833
OWN - NLM
STAT- MEDLINE
DCOM- 20151006
LR  - 20211021
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 396
IP  - 1-2
DP  - 2014 Nov
TI  - Trigonelline and diosgenin attenuate ER stress, oxidative stress-mediated damage 
      in pancreas and enhance adipose tissue PPARgamma activity in type 2 diabetic rats.
PG  - 161-74
LID - 10.1007/s11010-014-2152-x [doi]
AB  - Type 2 Diabetes mellitus (T2DM) is characterized by peripheral insulin 
      resistance, impaired insulin secretion, and reduced beta-cell mass. Mechanisms that 
      underlie beta-cell failure include glucotoxicity, lipotoxicity, endoplasmic 
      reticulum (ER) stress, and oxidative stress. This study was designed to assess 
      the protective effect of trigonelline and diosgenin against changes in ER 
      stress-associated apoptotic proteins CHOP, Caspase12, and Caspase3 and 
      antioxidant levels in pancreas as well as adipose tissue PPARgamma mRNA in T2DM rats. 
      Markers of diabetes and obesity such as serum glucose, insulin, free fatty acid 
      (FFA), TNF-alpha, IL-6, and leptin were also assessed. T2DM rats showed significantly 
      elevated levels of pancreatic ER stress proteins and lipid peroxidation, while 
      the antioxidants were significantly reduced. Histological examination also 
      confirmed T2DM-associated damage in pancreas. In addition, a significant increase 
      in serum FFA, TNF-alpha, IL-6, and decrease in leptin levels along with significantly 
      decreased adipose mass and reduced PPARgamma expression were observed in T2DM rats. 
      On the other hand, trigonelline and diosgenin treatment independently brought 
      about significant improvement in serum parameters, decrease in apoptotic ER 
      stress proteins, and reinforced antioxidant status in pancreas. Histological 
      examination of pancreas showed normal morphology. Treated groups also showed 
      increased adipose tissue mass and enhanced PPARgamma expression. Data from docking 
      studies indicated good interaction of both compounds with PPARgamma, and diosgenin 
      showed better binding efficiency. These findings suggest that the 
      insulin-sensitizing effects of trigonelline and diosgenin are mediated through 
      moderation of ER stress and oxidative stress in pancreas as well as by PPARgamma 
      activation in adipose tissue.
FAU - Tharaheswari, M
AU  - Tharaheswari M
AD  - Department of Biochemistry and Molecular Biology, School of Life Sciences, 
      Pondicherry University, Puducherry, India.
FAU - Jayachandra Reddy, N
AU  - Jayachandra Reddy N
FAU - Kumar, R
AU  - Kumar R
FAU - Varshney, K C
AU  - Varshney KC
FAU - Kannan, M
AU  - Kannan M
FAU - Sudha Rani, S
AU  - Sudha Rani S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140729
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Alkaloids)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - 0 (Leptin)
RN  - 0 (PPAR gamma)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3NQ9N60I00 (trigonelline)
RN  - K49P2K8WLX (Diosgenin)
SB  - IM
MH  - Adipose Tissue/*drug effects/metabolism
MH  - Alkaloids/chemistry/*pharmacology
MH  - Animals
MH  - Diabetes Mellitus, Experimental/drug therapy/metabolism
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Diet, High-Fat
MH  - Diosgenin/chemistry/*pharmacology
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Insulin/blood
MH  - Interleukin-6/blood
MH  - Leptin/blood
MH  - Male
MH  - Molecular Docking Simulation
MH  - Oxidative Stress/drug effects
MH  - PPAR gamma/chemistry/genetics/*metabolism
MH  - Pancreas/drug effects/pathology
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/blood
EDAT- 2014/07/30 06:00
MHDA- 2015/10/07 06:00
CRDT- 2014/07/30 06:00
PHST- 2014/04/16 00:00 [received]
PHST- 2014/07/11 00:00 [accepted]
PHST- 2014/07/30 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2015/10/07 06:00 [medline]
AID - 10.1007/s11010-014-2152-x [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2014 Nov;396(1-2):161-74. doi: 10.1007/s11010-014-2152-x. Epub 
      2014 Jul 29.