High-sucrose diet induces diabetic-like phenotypes and oxidative stress in Drosophila melanogaster: Protective role of Syzygium cumini and Bauhinia forficata.

Diet is a key component for development and longevity of organisms. Here, the fruit fly was used to evaluate the detrimental effects caused by consumption of high-sucrose diets (HSD), namely phenotypic responses linked to insulin signaling and oxidative stress. The protective effects of extracts from medicinal plants Syzygium cumini and Bauhinia forficata were investigated. HSD intake (15% and 30%) delayed the time to pupation and reduced the number of white pupae. In adult flies, the intake of diets was associated with mortality and increased levels of glucose+trehalose, triacylglycerols and hydrogen peroxide. Indeed, 30% HSD induced body-weight loss, mitochondrial dysfunction and changes in acetylcholinesterase, δ-aminolevulinate dehydratase and antioxidant enzymes activity. Catalase, superoxide dismutase, keap1, HSP70, dILP-5 and Insulin receptor mRNA levels were over-expressed in flies emerged from 30% HSD. The extract treatments blunted the developmental alterations elicited by diets. Syzygium cumini extract was more efficient than B. forficata in reducing hyperglycaemia, redox disturbances and the changes in mRNA expression of insulin receptor.

Fructose-induced inflammation, insulin resistance and oxidative stress: A liver pathological triad effectively disrupted by lipoic acid.

AIMS: Fructose administration induces hepatic oxidative stress, insulin resistance, inflammatory and metabolic changes. We tested their potential pathogenic relationship and whether these alterations can be prevented by R/S-α-lipoic acid. MAIN METHODS: Wistar rats received during 21days a commercial diet or the same diet supplemented with 10% fructose in drinking water without/with R/S-α-lipoic acid injection. After this period, we measured a) serum glucose, triglyceride, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), insulin glucose ratio (IGR) and Matsuda indexes and b) liver oxidative stress, inflammatory markers and insulin signaling pathway components. KEY FINDINGS: Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR, IGR and lower Matsuda indices compared to control animals, together with increased oxidative stress markers, TNFα, IL1ß and PAI-1 gene expression, and TNFα and COX-2 protein content. Whereas insulin receptor level was higher in fructose fed rats, their tyrosine-residue phosphorylation was lower. IRS1/IRS2 protein levels and IRS1 tyrosine-phosphorylation rate were lower in fructose fed rats. All changes were prevented by R/S-α-lipoic acid co-administration. SIGNIFICANCE: Fructose-induced hepatic oxidative stress, insulin resistance and inflammation form a triad that constitutes a vicious pathogenic circle. This circle can be effectively disrupted by R/S-α-lipoic acid co-administration, thus suggesting mutual positive interaction among the triad components.

IGF-I and INS receptor expression in the salivary glands of diabetic Nod mice submitted to long-term insulin treatment.

This work aimed to characterize the IGF-I and INS receptor expression in the salivary glands of Nod mice, correlating to therapeutic effects of insulin treatment on these receptors. Nod mice were divided into: Groups 1 and 2 (diabetic), Groups 3 and 4 (diabetic with insulin treatment) and Group 5 (non-diabetic). Fragments from the salivary glands were processed for immunohistochemical analysis. The results showed that the prolonged diabetic state led to a steadily increased IGF-I receptor expression. INS receptor expression was gradually decreased. It was concluded that not only was the IGF-I receptor expression affected by the diabetic state but also the INS receptor expression. The period of the diabetic state was directly related to changes in the expression of these receptors. In spite of the insulin treatment having recovered the glycaemic levels, the expression of INS and the IGF-I receptors did not reach the standard level, which certainly hampered glandular function.

Characteristics of insulin receptors in a clonal line of rat pituitary tumor cells in culture.

The presence of insulin binding sites in a clonal line of cells from rat pituitary tumor (GH1 cells) is described. The binding of insulin was a reversible and specific process. Binding of 125I-insulin to GH1 cells was inhibited by unlabeled insulin and to a minor extent, by proinsulin and desalanine insulin in direct proportion to their biological activities. Trypsin abolished the insulin binding to the cells. Twelve hours incubation of cells with insulin (5 microM) reduced in a 45% of the number of binding sites for the hormone. 125I-insulin bound to GH1 cells dissociated with a t 1/2 of 8 min. At 24 C labeled insulin was degraded by GH1 cells. No degradation was detected at 6 C. Unlabeled insulin inhibited most of the degradation of 125I-insulin, suggesting that degradation resulted from a saturable process. At steady-state, radioactive degradation products as well as 125I-insulin were recovered from GH1 cells.