Effect of Carica papaya on IRS-1/Akt Signaling Mechanisms in High-Fat-Diet–Streptozotocin-Induced Type 2 Diabetic Experimental Rats: A Mechanistic Approach

Abstract

Despite rigorous endeavors, existing attempts to handle type 2 diabetes (T2DM) are still a long way off, as a substantial number of patients do not meet therapeutic targets. Insulin resistance in skeletal muscle is discerned as a forerunner in the pathogenesis of T2DM and can be detected years before its progress. Studies have revealed the antidiabetic properties of Carica papaya (C. papaya), but its molecular mechanism on insulin receptor substrate-1 (IRS-1)/Akt signaling mechanisms is not yet known. The present study aimed to evaluate the role of C. papaya on IRS1 and Akt in high-fat-diet–streptozotocin-induced type 2 diabetic rats and also to analyze the bioactive compounds of C. papaya against IRS-1 and Akt via in silico analysis. Ethanolic extract of the leaves of C. papaya (600 mg/kg of body weight) was given daily for 45 days postinduction of T2DM up to the end of the study. Gluconeogenic enzymes, glycolytic enzymes, gene expression, and immunohistochemical analysis of IRS-1 and Akt in skeletal muscle were evaluated. C. papaya treatment regulated the levels of gluconeogenic and glycolytic enzymes and the levels of IRS-1 and Akt in skeletal muscle of type 2 diabetic animals. In silico studies showed that trans-ferulic acid had the greatest hit rate against the protein targets IRS-1 and Akt. C. papaya restored the normoglycemic effect in diabetic skeletal muscle by accelerating the expression of IRS-1 and Akt.

Amazonian useful plants described in the book “Le Pays des Amazones” (1885) of the Brazilian propagandist Baron de Santa-Anna Nery: a historical and ethnobotanical perspective

“… ipê-tabaco 106 Stem bark Native Purgative; dust causes sneezing Antihyperuricemic, anti-inflammatory [ 48 , 49 ]; antinociceptive [ 50 ] Tecoma sp. ipê branco 106 Stem bark Naturalized Purgative Antidiarrheal [ 51 ] Caricaceae Carica papaya L. mamoeiro 102 Unripe fruit Naturalized Vermifuge Anthelmintic † [ 52 , 53 ]; hypoglycemic [ 54 ]; immunomodulatory [ 55 ]; antithrombocytopenic [ 56 ] Chrysobalanaceae Couepia sp. (= Pleraginea sp.)…”

Phenolic Constituents from Black Quinoa Alleviate Insulin Resistance in HepG2 Cells via Regulating IRS1/PI3K/Akt/GLUTs Signaling Pathways

“…HK, a constitutive enzyme with a high affinity, is the primary enzyme of the glycolysis process. Normally, it can phosphorylate the glucose of cells to glucose-6-phosphate in time, creating a concentration gradient that facilitates the entry of residual glucose into blood. , Then, glucose-6-phosphate continues to participate in the glycolysis pathway or glycogen synthesis, helping to maintain the blood glucose homeostasis. A previous study reported that p-coumaric acid can reduce blood glucose levels by reversing the activity reduction of HK and glucose-6-phosphate dehydrogenase in the liver during IR .…”

Hypoglycemic Potential of Carica papaya in Liver Is Mediated through IRS-2/PI3K/SREBP-1c/GLUT2 Signaling in High-Fat-Diet-Induced Type-2 Diabetic Male Rats

“…In our earlier research, we found that C. papaya can restore glycemic control by exhibiting insulinemic action in T2DM skeletal muscle by increasing the levels of IR, IRS-1, Akt, and GLUT-4. The potential influence of C. papaya on insulin-signaling molecules in skeletal muscle was shown in a HFD-STZ-induced T2DM model [ 55 , 56 ]. In light of this, we centered on oxidative stress, gluconeogenic-glycolytic enzymes, and the expression of genes in the hepatic tissues of diabetic rats, and assessed the effect of C. papaya on hepatic insulin resistance using in vivo and in silico models.…”