Therapeutic potential of pectin from various sources against diabetes mellitus in rats: AKT/PI3K/GSK-3β/CREB signaling pathways, inflammation, oxidative stress and genotoxicity crosstalk.

Background: Diabetes mellitus type 2 (DMT2) is a chronic metabolic disorder caused by a disruption or resistance in insulin secretion. AKT /PI3K, GSK-3β and CREB signaling pathways influence insulin sensitivity and glucose metabolism. Purpose: This study aimed to compare the therapeutic impact of pectin extracted from different sources (lemon, orange and grapefruit peels) against diabetic rats. Methods: Fourier transform infrared spectroscopy (FT-RI) and Proton Nuclear Magnetic Resonance (1H-NMR) analysis of pectin were done. Treatments were administered daily for one month (500 mg/kg) post diabetes induction via a single dose of streptozotocin (STZ) (40 mg/kg) considering Metformin as a reference drug (250 mg/kg). Biochemical, mutagenicity and genotoxicity analyses were assessed. Results: The FT-IR and1H-NMR revealed that lemon pectin had a strong peak at ≈3.7 ppm. Orange pectin showed a moderate peak at ≈3.7 ppm, and grapefruit pectin showed a weak peak at ≈3.7 ppm. Diabetic rats showed alterations in glucose, insulin, liver function enzymes, urea, oxidative stress indices, IL-6, TNF-α, AKT, PI3K levels and GSK-3β and cAMP responsive element binding protein 1(CREB) genes expression. Changes in micronuclei of polychromatic erythrocytes, chromosomal aberrations, sperm abnormalities and the histopathology of liver and pancreas were also observed. Pectin treatments declared a notable amelioration in glucose and insulin levels as well as the other selected parameters. Conclusion: Pectin extracted from lemon, orange and grapefruit peels showed a promising therapeutic impact against DMT2. High degree of esterification in lemon pectin may explore its potent effect via regulating glucose, α-amylase and the metabolic genes expression pathways. Orange pectin exhibits the strongest anti-mutagenic properties. Together, citrus pectin may be considered as a nutraceutical agent against diabetes.