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Gene & Protein in Disease Effect of phytochemicals in diabetes

The difference in potential energy of the AMPK-ligand cancer, and cardiovascular problems through downward
complex may be due to the distance and disparity in the cascading molecules and related mechanism. Therefore, its
attractive and weaker interactions such as H-bonding, nature of action can be validated further by wet laboratory
electrostatic forces, hydrophobic interaction, or experiments and clinical trials. Moreover, some literature
unfavorable bonding. The result provides evidence that shows that vindoline and α/β-tubulin (PDB: 1Z2B) have
AMPK1 and AMPK2 complexes have identical specific a binding affinity of −7.28 kcal/mol. Therefore, vindoline
activity but differences in binding affinity of ligands and can improve the protection mechanism of plants and
also have differential substrate preference. All the qualified have inhibitory outcomes on cancer cells. Alkaloids have
ligands/leads have correlated substrate specificity with antioxidant properties and can decrease glucotoxicity and
both targets because the alpha-1 and alpha-2 subunits reactive oxygen species (ROS) generation by quenching
of AMPK have well-built homology (77% resemblance ROS and suppressing oxidative phosphorylation in stress
in amino acids) around the substrate binding groves conditions by exciting AMPK1 .
[58]
(Thr172) and contribute similarly to the total AMPK AMPK2 is greatly expressed in cardiac muscle, skeletal
action . Dissimilarity in substrate liking based on binding muscles, and liver , and contributes < 10% activity of
[10]
[11]
energy value may be due to a difference in the degree of AMPK . AMPK2 enzyme regulates metabolic health
[10]
phosphorylation . Diversity in the mechanism of action by cellular energy homeostasis, promoting glucose and
[52]
of both subunits is due to differences in downstream targets fatty acid uptake, improving insulin sensitivity, reducing
of the AMPK cascade [10,52] . AMPK1 and AMPK2 enzymes insulin resistance, recycling insulin receptors (INSR),
are involved in the direct phosphorylation of metabolic and regulating GLUT4 transport . Also, activated
[17]
enzymes and transcription regulation and have distinct AMPK2 phosphorylates glycolysis pathway machinery
biological functions ; therefore, AMPK is known to be 6-phosphofructokinase-2 (PFKB2), and fructose-2,6-
[17]
an important first-line target for the treatment of Type II biphosphatase 3 (PFKB3). In the liver, it stimulates
diabetes and other diseases .
[55]
glucose homeostasis by phosphorylating CREB-regulated
AMPK1 is widely present and expressed, regulates transcription coactivator 2 (CRTC2)/target of rapamycin
intracellular signaling through phosphorylation, and 2 (TORC2) . Thus, AMPK2 activation by biomolecules
[17]
accounts for more than 90% of the AMPK activity [10,11] . reduces hepatic glucose production, increases glucose
The current study result shows that the C. roseus alkaloids utilization in hepatocytes, and amplifies insulin-mediated
are excellent indirect AMPK1 stimulators and activate peripheral glucose absorption by GLUT4 in skeletal
the target by the release of sarcoplasmic calcium ion muscle and fat cells and as a result, decreases blood
and disturbs energy balance which leads to increased sugar concentration [1,17,19-21,54] . Based on the literature,
AMP: ATP ratio . It is known that AMPK1 regulates the metabolic pathway of AMPK2 was highlighted in
[56]
enzymes of glucose metabolism , and insulin release , Figure 3B and its nature of action can be confirmed further
[13]
[16]
but is not able to generate a sufficient signal for glucose by wet laboratory experiments and clinical trials.
uptake. However, in the case of low-intensity twitch C. roseus ethanolic extract appreciably curtailed the
contraction, it promotes glucose uptake up to 60% by
glucose transporter 1 (GLUT1) and has a limited role in elevated blood sugar level in addition to uplifting significantly
glucose metabolism . Moreover, AMPK1 plays a major antioxidant security systems and helping in the revival of
[56]
[58]
role in safeguarding cells from stresses that bring out ATP beta cells . An in silico study of alkaloid vindoline showed
depletion through turning off ATP-consuming biosynthetic that it controls hyperglycemia and other glucotoxicity-
induced pathogenesis by acting on multiple targets (AMPK,
pathways . In addition, it engages in the mammalian peroxisome proliferator-activated receptor γ [PPARγ],
[12]
target of rapamycin (mTOR) signaling pathway , cytokine dipeptidyl peptidase 4 [DPP , and α-glucosidase) .
[15]
4]
[59]
secretion, macrophage activation through regulation of
arginine metabolism key enzymes, prostaglandin synthesis, Vindoline was examined on Wistar rats and the outcome
immune suppression, differentiation of MDSC [14,16] , showed that vindoline reduces significantly fasting blood
prohibiting skeletal muscle hypertrophy, etc. [15,57] . The glucose level (FBG) (P < 0.05) and lessens hyperglycemia-
metabolic pathway was highlighted in Figure 3A based on the generated liver, kidney damage, and improves the in vitro
[60]
literature. According to the computational docking studies insulin discharge in pancreatic tissues .
resulted in high binding affinity between the target and Chronic AMPK2 stimulation reduces or inhibits
[61]
ligands in this study, it is predicted that by activating AMPK1 ACC activity and HMG-CoA reductase , induces fatty
the biomolecules (vindoline, vindolinine, (+)-vindorosine, acid oxidation, and suppresses expression of lipogenic
Cr-1, and Cr-2) can protect beta cells of pancreas and enzymes, leading to a decrease of membrane cholesterol
control diseases related to cellular stress conditions, (~10%) and triglyceride (~45%) levels , restoring F-actin
[62]
Volume 2 Issue 3 (2023) 10 https://doi.org/10.36922/gpd.0927