Carica papaya Reduces Muscle Insulin Resistance via IR/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and Streptozotocin-Induced Type-2 Diabetic Rats

Roy, Jeane Rebecca; Janaki, Coimbatore Sadagopan; Jayaraman, Selvaraj; Balaji, Thotakura; Vijayamalathi, Madhavan; Veeraraghavan, Vishnu Priya

doi:10.3390/antiox11102081

Cited by 10 publications

(5 citation statements)

References 56 publications

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“…4 a). IR and GLUT4 muscle expression was elevated by ethanolic PL extracts in diabetic mice, as demonstrated by Roy et al [ 37 ]. This effect may be due to papaya's phenols and flavonoids [ 30 ].…”

Section: Discussionmentioning

confidence: 71%

Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice

Nyakundi,

Wall,

Yang

2024

BMC Complement Med Ther

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Prediabetes is characterized by a cluster of glycemic parameters higher than normal but below the threshold of type 2 diabetes mellitus (T2DM). In recent years, phytochemical-rich plant extracts have gained popularity as therapeutic agents for metabolic disorders. This study investigated the effects of papaya leaf (PL) juice supplementation on blood glucose levels in diet-induced obese and prediabetic adult mice. B65JL F1 mice (n = 20) at 12–14 months old were fed a high fat/sugar diet (HFHS) for 120 days. Mice were switched to restricted rodent chow of 3 g feed/30 g body weight/day, supplemented with 3 g/100 mL PL juice for 30 days. HFHS diet remarkably increased fasting plasma glucose levels from 114 ± 6.54 mg/dL to 192.7 ± 10.1 mg/dL and body weight from 32.5 ± 1.6 to 50.3 ± 4.1 g. HFHS diet results in hyperglycemia, insulin resistance, hyperlipidemia, and liver steatosis. The combination of PL juice and restricted diet significantly reduced body weight and fasting blood glucose levels to 43.75 ± 1.4 g and 126.25 ± 3.2 mg/dl, respectively. Moreover, PL juice with a restricted diet significantly improved lipid profile: cholesterol from 204 to 150 mg/dL, LDL-c from 110.4 to 50 mg/dL, and triglyceride from 93.7 to 60 mg/dL. Additionally, PL juice combined with a restricted diet significantly reduced adiposity, reversed fatty liver, and restored skeletal muscle Glut4 and phosphorylated (p-AKT (ser473). This study demonstrated that supplementation of PL juice with a restricted diet was more effective than a restricted diet alone in reversing major symptoms related to prediabetic and obesity conditions.

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Section: Discussionmentioning

confidence: 71%

Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice

Nyakundi,

Wall,

Yang

2024

BMC Complement Med Ther

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Roy

Janaki

Jayaraman

et al. 2023

Toxics

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Regardless of socioeconomic or demographic background, the prevalence of type 2 diabetes mellitus, which affects more than half a billion people worldwide, has been steadily increasing over time. The health, emotional, sociological, and economic well-being of people would suffer if this number is not successfully handled. The liver is one of the key organs accountable for sustaining metabolic balance. Elevated levels of reactive oxygen species inhibit the recruitment and activation of IRS-1, IRS-2, and PI3K-Akt downstream signaling cascade. These signaling mechanisms reduce hepatic glucose absorption and glycogenesis while increasing hepatic glucose output and glycogenolysis. In our work, an analysis of the molecular mechanism of Carica papaya in mitigating hepatic insulin resistance in vivo and in silico was carried out. The gluconeogenic enzymes, glycolytic enzymes, hepatic glycogen tissue concentration, oxidative stress markers, enzymatic antioxidants, protein expression of IRS-2, PI3K, SREBP-1C, and GLUT-2 were evaluated in the liver tissues of high-fat-diet streptozotocin-induced type 2 diabetic rats using q-RT-PCR as well as immunohistochemistry and histopathology. Upon treatment, C. papaya restored the protein and gene expression in the liver. In the docking analysis, quercetin, kaempferol, caffeic acid, and p-coumaric acid present in the extract were found to have high binding affinities against IRS-2, PI3K, SREBP-1c, and GLUT-2, which may have contributed much to the antidiabetic property of C. papaya. Thus, C. papaya was capable of restoring the altered levels in the hepatic tissues of T2DM rats, reversing hepatic insulin resistance.

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“…"Metabolic syndrome" ailments such as diabetes destroy the balance of glucose homeostasis and cause systematic endocrine disorder, but can be corrected by the upregulation of the GLUT4 gene. A study has shown that the ethanolic extract of papaya leaf can reduce muscle insulin resistance by upregulating glut-4 in high-fat-dietand streptozotocin-induced type 2 diabetes in rats [54]. The effects of aqueous guava leaf extract on insulin resistance and glucose transportation were evaluated in an insulinresistant C57BL/6J mice model induced by a high-fructose-high-fat diet [55].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Green and Yellow Papaya (Carica papaya) for Anti-Diabetic Activity in Liver and Myoblast Cells and Wound-Healing Activity in Fibroblast Cells

Beg

Rafie

et al. 2023

Nutrients

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Obesity and diabetes, often characterized as “metabolic syndrome”, have been recognized as two of the most important public health issues worldwide. The objective of the present research was to evaluate green and yellow papaya for anti-oxidation and anti-diabetic properties. Leaves, skin, pulp, and seed samples from papayas were freeze-dried and then extracted in water or 80% methanol. The extracts were used to determine total polyphenolic content and anti-oxidation activities, and to determine biological activities, including glucose uptake, Glut-2 expression, triglyceride reduction, and wound-healing activity. Our data demonstrated that methanol and water extracts of green and yellow papaya have similar concentrations of polyphenols in skin (10–20 mg/g dry powder), leaf (25–30 mg/g dry powder), and pulp (1–3 mg/g dry powder) fractions. However, both methanol and water extracts of seeds from yellow papaya have substantially higher concentrations of polyphenols compared to green papaya. Both water and methanol extracts of yellow papaya exhibited higher anti-oxidation activity compared to green papaya in skin (50–60%), pulp (200–300%), and seeds (10–800%). Old leaves also showed greater anti-oxidation activity (30–40%) compared to new leaves. Pulp extracts from both yellow and green papaya stimulated greater glucose uptake, but only pulp from green papaya stimulated glucose uptake in muscle cells. Similarly, pulp extract stimulated glucose transporter Glut-2 expression in liver cells. The skin, pulp, and seeds of green or yellow papaya showed triglyceride-lowering activity in liver cells by 60–80%, but samples taken from yellow papaya had a more potent effect. Seeds from both green and yellow papaya significantly stimulated the migration of fibroblasts in the wounded area by 2–2.5-fold compared to the untreated control. Consistent with these data, seeds from both green and yellow papaya also significantly stimulated collagen synthesis in fibroblast cells by almost 3-fold. In conclusion, our data indicate that different parts of papaya produce stimulatory effects on glucose uptake, Glut-2 expression, TG reduction, and wound-healing activities. This study concludes that different parts of the papaya can be beneficial for preventing diabetes and diabetes-related wound healing.

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Carica papaya Reduces Muscle Insulin Resistance via IR/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and Streptozotocin-Induced Type-2 Diabetic Rats

Cited by 10 publications

References 56 publications

Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice

Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice

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

Characterization of Green and Yellow Papaya (Carica papaya) for Anti-Diabetic Activity in Liver and Myoblast Cells and Wound-Healing Activity in Fibroblast Cells

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