Pancreastatin inhibitor, PSTi8 ameliorates metabolic health by modulating AKT/GSK-3β and PKCλ/ζ/SREBP1c pathways in high fat diet induced insulin resistance in peri-/post-menopausal rats. 2019

Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.

Increase in the prevalence of insulin resistance (IR) in peri-/post-menopause women is mainly due to hormone deficiency and lifestyle. PSTi8 (PEGKGEQEHSQQKEEEEEMAV-amide) is a pancreastatin inhibitor peptide which showed potent antidiabetic activity in genetic and lifestyle induced type 2 diabetic mice. In the present work, we have investigated the antidiabetic activity of PSTi8 in rat models of peri-/post-menopausal IR. 4-vinylcyclohexenediepoxide treated and ovariectomized rats were fed with high fat diet for 12 weeks to develop the peri-/post-menopausal IR. PSTi8 peptide was administered after the development of peri-/post-menopausal IR rats. PSTi8 (1 mg/kg, i.p) improved the glucose homeostasis which is characterized by elevated glycogenesis, enhanced glycolysis and reduced gluconeogenesis. PSTi8 suppressed palmitate- and PST- induced IR in HepG2 cells. PSTi8 treatment enhanced energy expenditure in peri-/post-menopausal IR rats. PSTi8 treatment increased insulin sensitivity in peri-/post-menopausal IR rats, may be mediated by modulating IRS1-2-phosphatidylinositol-3-kinase-AKT-GSK3β and IRS1-2-phosphatidylinositol-3-kinase-PKCλ/ζ-SREBP1c signaling pathways in the liver. PSTi8 can act as a potential therapeutic peptide for the treatment of peri-/post-menopausal IR.

UI MeSH Term Description Entries
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D004041 Dietary Fats Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. Fats, Dietary,Dietary Fat,Fat, Dietary
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071679 Glycogen Synthase Kinase 3 beta A glycogen synthase kinase-3 type enzyme that functions in ENERGY METABOLISM; EMBRYONIC DEVELOPMENT; and NEUROGENESIS. It is also involved in PROTEIN BIOSYNTHESIS and regulates cell growth and proliferation as a component of the WNT SIGNALING PATHWAY and other signaling pathways. Certain polymorphisms in the GSK3B gene have been associated with PARKINSON DISEASE; ALZHEIMER DISEASE; and BIPOLAR DISORDER. GSK-3beta,GSK3B Protein,GSK3beta,GSK 3beta
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017698 Postmenopause The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life. Post-Menopause,Post-menopausal Period,Postmenopausal Period,Period, Post-menopausal,Period, Postmenopausal,Post Menopause,Post menopausal Period,Post-Menopauses

Related Publications

Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
November 2023, Amino acids,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
September 2019, Die Pharmazie,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
April 2023, European journal of pharmacology,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
January 2023, Peptides,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
January 2015, Evidence-based complementary and alternative medicine : eCAM,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
January 2022, Life sciences,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
March 2022, Experimental gerontology,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
March 2013, World journal of gastroenterology,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
March 2023, Life sciences,
Guru R Valicherla, and Anand P Gupta, and Zakir Hossain, and Mohammed Riyazuddin, and Anees A Syed, and Athar Husain, and Shibani Lahiri, and Kandarp M Dave, and Jiaur R Gayen
September 2022, Molecules (Basel, Switzerland),
Copied contents to your clipboard!