PMID- 34946771
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20220214
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 26
IP  - 24
DP  - 2021 Dec 20
TI  - Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating 
      IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach.
LID - 10.3390/molecules26247689 [doi]
LID - 7689
AB  - Type-2 diabetes mellitus (T2DM), the leading global health burden of this century 
      majorly develops due to obesity and hyperglycemia-induced oxidative stress in 
      skeletal muscles. Hence, developing novel drugs that ameliorate these 
      pathological events is an immediate priority. The study was designed to analyze 
      the possible role of Stevioside, a characteristic sugar from leaves of Stevia 
      rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of 
      obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered 
      diabetic by administration of high fat diet (HFD) and sucrose for 60 days were 
      orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were 
      estimated including fasting blood glucose (FBG), serum lipid profile, oxidative 
      stress markers, antioxidant enzymes and expression of insulin signaling molecules 
      in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and 
      insulin tolerances in diabetic rats and restored their elevated levels of FBG, 
      serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, 
      Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen 
      peroxide (H(2)O(2)) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, 
      GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), 
      insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside 
      enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting 
      glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to 
      metformin. Results of molecular docking analysis evidenced the higher binding 
      affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress 
      and promotes glucose uptake in diabetic gastrocnemius muscles by activating 
      IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched 
      those of the in vivo study. Hence, Stevioside could be considered as a promising 
      phytomedicine to treat T2DM.
FAU - Deenadayalan, Abilasha
AU  - Deenadayalan A
AD  - Department of Anatomy, Saveetha Institute of Medical & Technical Sciences, 
      Chennai 602 105, India.
AD  - Department of Anatomy, Asan Memorial Dental College and Hospitals, Asan Nagar, 
      Chengalpattu, Chennai 602 105, India.
FAU - Subramanian, Vijayalakshmi
AU  - Subramanian V
AD  - Department of Anatomy, Saveetha Institute of Medical & Technical Sciences, 
      Chennai 602 105, India.
FAU - Paramasivan, Vijayalakshmi
AU  - Paramasivan V
AD  - Department of Pharmacology, Asan Memorial Dental College and Hospitals, Asan 
      Nagar, Chengalpattu, Chennai 602 105, India.
FAU - Veeraraghavan, Vishnu Priya
AU  - Veeraraghavan VP
AD  - Department of Biochemistry, Saveetha Dental College & Hospital, Saveetha 
      Institute of Medical & Technical Sciences, Chennai 600 077, India.
FAU - Rengasamy, Gayathri
AU  - Rengasamy G
AD  - Department of Biochemistry, Saveetha Dental College & Hospital, Saveetha 
      Institute of Medical & Technical Sciences, Chennai 600 077, India.
FAU - Coiambatore Sadagopan, Janaki
AU  - Coiambatore Sadagopan J
AD  - Department of Anatomy, Bhaarat Medical College, Selaiyur, Chennai 600 073, India.
FAU - Rajagopal, Ponnulakshmi
AU  - Rajagopal P
AD  - Department of Central Research Laboratory, Meenakshi Ammal Dental College and 
      Hospitals, Chennai 600 095, India.
FAU - Jayaraman, Selvaraj
AU  - Jayaraman S
AD  - Department of Biochemistry, Saveetha Dental College & Hospital, Saveetha 
      Institute of Medical & Technical Sciences, Chennai 600 077, India.
LA  - eng
PT  - Journal Article
DEP - 20211220
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Diterpenes, Kaurane)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Glucosides)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (Slc2a4 protein, rat)
RN  - 0YON5MXJ9P (stevioside)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Experimental/drug therapy/*metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/*metabolism
MH  - Diterpenes, Kaurane/*pharmacology
MH  - Glucose Transporter Type 4/*metabolism
MH  - Glucosides/*pharmacology
MH  - Insulin Receptor Substrate Proteins/*metabolism
MH  - *Insulin Resistance
MH  - Male
MH  - Muscle, Skeletal/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Insulin/*metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC8707280
OTO - NOTNLM
OT  - Stevioside
OT  - antioxidants
OT  - gastrocnemius muscle
OT  - insulin resistance
OT  - insulin signaling
OT  - oxidative stress
OT  - type-2 diabetes
COIS- The authors declare no conflict of interest.
EDAT- 2021/12/25 06:00
MHDA- 2022/02/15 06:00
PMCR- 2021/12/20
CRDT- 2021/12/24 01:12
PHST- 2021/10/20 00:00 [received]
PHST- 2021/12/16 00:00 [revised]
PHST- 2021/12/17 00:00 [accepted]
PHST- 2021/12/24 01:12 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
PHST- 2021/12/20 00:00 [pmc-release]
AID - molecules26247689 [pii]
AID - molecules-26-07689 [pii]
AID - 10.3390/molecules26247689 [doi]
PST - epublish
SO  - Molecules. 2021 Dec 20;26(24):7689. doi: 10.3390/molecules26247689.