Protective effect of nimbolide against streptozotocin induced gestational diabetes mellitus in rats via alteration of inflammatory reaction, oxidative stress, and gut microbiota.

BACKGROUND: Gestational diabetes mellitus (GDM) is a significant pregnancy-related condition, which showed effect on the development of fetal. Anti-inflammatory and antioxidant therapy commonly used for the treatment of GDM. Nimbolide already confirmed their anti-inflammatory and anti-oxidant effect against various animal disease model. Our objective in this research is to investigate the protective effect of nimbolide against STZ induced GDM and elucidate the mechanism. METHODS: In this experimental study, pregnant female Wistar rats were used and STZ (40 mg/kg) was used to induce the GDM. Blood glucose level (BGL), body weight and plasma insulin were assessed at regular time (gestational day 0, 9, and 18). Water intake, food intake, fecal and urine output were also estimated. In the female rats, hemoglobin (Hb), glycalated hemoglobin (HbA1c), hepatic glycogen, fructosamine, adiponectin, leptin, lipid, antioxidant and inflammatory cytokines parameters were estimated. In the fetuses, the fetues weight, implementation loss, and fetal weight were estimated. At the completion of the protocol, biochemical parameters were calculated. Gut microbiota was estimated in end of the study. RESULTS: Nimbolide treatment significantly (p < .001) improved the fetuses level and suppressed the fetal weight and implantation loss. Nimbolide treatment significantly (p < .001) suppressed the BGL and enhanced the body weight, insulin level. Nimbolide treatment suppressed the water intake, food intake, urinary and fecal output. Nimbolide significantly (p < .001) suppressed the fructosamine, leptin and enhanced the adiponectin level. Nimbolide treatment significantly (p < .001) decreased the malonaldehyde (MDA) level and boosted the total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and catalase (CAT); suppressed the level of TNF-α, IL-1ß, IL-6, and boosted the level of IL-10. Furthermore, nimbolide treatment reversed the gut microbiota alteration induced via STZ in female rats. At the phylum level, the Firmicutes and Bacteroidetes relative abundance was altered via nimbolide treatment. The ratio of F/B boosted in GDM group and nimbolide treatment significantly (p < .001) suppressed. Nimbolide considerably suppressed the firmicutes and enhanced the Bacteroidetes, CAG-352, Lacnospirace. CONCLUSION: Based on the findings, we may conclude that nimbolide protects the pregnant rats from GDM via alteration of inflammation, oxidative stress, and gut microbiota.

Effects of coconut oil long-term supplementation in Wistar rats during metabolic syndrome - regulation of metabolic conditions involving glucose homeostasis, inflammatory signals, and oxidative stress.

This study was designed to evaluate the long-term effects of Fructose (20%) feeding in rats, simulating metabolic syndrome (MetS), and the effects of coconut oil (C.O.) supplementation when administered in a MetS context. MetS is a cluster of systemic conditions that represent an increased chance of developing cardiovascular diseases and type 2 diabetes in the future. C.O. has been the target of media speculation, and recent studies report inconsistent results. C.O. improved glucose homeostasis and reduced fat accumulation in Fructose-fed rats while decreasing the levels of triglycerides (TGs) in the liver. C.O. supplementation also increased TGs levels and fructosamine in serum during MetS, possibly due to white adipose tissue breakdown and high fructose feeding. Pro-inflammatory cytokines IL-1ß and TNF-α were also increased in rats treated with Fructose and C.O. Oxidative stress marker nitrotyrosine is increased in fructose-fed animals, and C.O. treatment did not prevent this damage. No significant changes were observed in lipoperoxidation marker 4-Hydroxynonenal; however, fructose feeding increased total conjugated dienes and caused conjugated dienes to switch their conformation from cis-trans to trans-trans, which was not prevented by C.O. treatment. Potential benefits of C.O. have been reported with inconsistent results, and indeed we observed some benefits of C.O. supplementation in aiding weight loss, fat accumulation, and improving glucose homeostasis. Nonetheless, we also demonstrated that long-term C.O. supplementation could present some problematic effects with higher risk for individuals suffering MetS, including increased TGs and fructosamine levels and conformational changes in dienes.

Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome.

Numerous studies on metabolic syndrome (MetSyn), a cluster of metabolic abnormalities, have demonstrated its profound impact on cardiovascular and blood microvascular health; however, the effects of MetSyn on lymphatic function are not well understood. We hypothesized that MetSyn would modulate lymphatic muscle activity and alter muscularized lymphatic function similar to the impairment of blood vessel function associated with MetSyn, particularly given the direct proximity of the lymphatics to the chronically inflamed adipose depots. To test this hypothesis, rats were placed on a high-fructose diet (60%) for 7 wk, and their progression to MetSyn was assessed through serum insulin and triglyceride levels in addition to the expression of metabolic and inflammatory genes in the liver. Mesenteric lymphatic vessels were isolated and subjected to different transmural pressures while lymphatic pumping and contractile parameters were evaluated. Lymphatics from MetSyn rats had significant negative chronotropic effects at all pressures that effectively reduced the intrinsic flow-generating capacity of these vessels by ∼50%. Furthermore, lymphatics were remodeled to a significantly smaller diameter in the animals with MetSyn. Wire myograph experiments demonstrated that permeabilized lymphatics from the MetSyn group exhibited a significant decrease in force generation and were less sensitive to Ca(2+), although there were no significant changes in lymphatic muscle cell coverage or morphology. Thus, our data provide the first evidence that MetSyn induces a remodeling of collecting lymphatics, thereby effectively reducing their potential load capabilities and impairing the intrinsic contractility required for proper lymph flow.

Dietary fructose and glucose differentially affect lipid and glucose homeostasis.

Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial triglyceride (TG) levels and has little effect on serum glucose concentrations, whereas dietary glucose has the opposite effects. When dietary glucose and fructose have been directly compared at approximately 20-25% of energy over a 4- to 6-wk period, dietary fructose caused significant increases in fasting TG and LDL cholesterol concentrations, whereas dietary glucose did not, but dietary glucose did increase serum glucose and insulin concentrations in the postprandial state whereas dietary fructose did not. When fructose at 30-60 g ( approximately 4-12% of energy) was added to the diet in the free-living state, there were no significant effects on lipid or glucose biomarkers. Sucrose and high-fructose corn syrup (HFCS) contain approximately equal amounts of fructose and glucose and no metabolic differences between them have been noted. Controlled feeding studies at more physiologic dietary intakes of fructose and glucose need to be conducted. In our view, to decrease the current high prevalence of obesity, dyslipidemia, insulin resistance, and diabetes, the focus should be on restricting the intake of excess energy, sucrose, HFCS, and animal and trans fats and increasing exercise and the intake of vegetables, vegetable oils, fish, fruit, whole grains, and fiber.

Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice.

OBJECTIVE: Effective approaches should be established to prevent the onset of type 2 diabetes mellitus, which has been increasing in developed countries. The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity. METHODS: C57BL/KsJ-db/db (db/db) diabetic obese mice and C57BL/KsJ-db/+m (db/+m) control mice were fed a diet containing 0% w/w CLPr (0% CLPr), 0.5% w/w CLPr (0.5% CLPr), or 1.0% w/w CLPr (1.0% CLPr) from age 3 wk to age 6 wk. Levels of blood glucose were measured at 4 and 5 wk of age. The animals were sacrificed and the levels of blood glucose and fructosamine were measured at 6 wk of age. RESULTS: The levels of blood glucose and fructosamine were higher in the db/db mice than in the db/+m mice fed a diet containing 0%, 0.5%, or 1.0% CLPr. In the db/+m mice, the levels of blood glucose or fructosamine were not significantly different across animals fed 0% CLPr, 0.5% CLPr, and 1.0% CLPr. In the db/db mice, however, a diet containing 0.5% or 1.0% CLPr decreased the levels of blood glucose and fructosamine compared with that containing 0% CLPr without significant effects on body weights or food consumption. CONCLUSION: Dietary supplementation with CLPr can dose-dependently prevent the development of hyperglycemia in diabetic obese mice. The dietary intake of food or drinks produced from cacao beans might be beneficial in preventing the onset of type 2 diabetes mellitus.

1-Amino-1-deoxy-D-fructose ("fructosamine") and its derivatives.

Fructosamine has long been considered as a key intermediate of the Maillard reaction, which to a large extent is responsible for specific aroma, taste, and color formation in thermally processed or dehydrated foods. Since the 1980s, however, as a product of the Amadori rearrangement reaction between glucose and biologically significant amines such as proteins, fructosamine has experienced a boom in biomedical research, mainly due to its relevance to pathologies in diabetes and aging. In this chapter, we assess the scope of the knowledge on and applications of fructosamine-related molecules in chemistry, food, and health sciences, as reflected mostly in publications within the past decade. Methods of fructosamine synthesis and analysis, its chemical, and biological properties, and degradation reactions, together with fructosamine-modifying and -recognizing proteins are surveyed.

Conversion of a synthetic fructosamine into its 3-phospho derivative in human erythrocytes.

Intact human erythrocytes catalyse the conversion of fructose into fructose 3-phosphate with an apparent K(m) of 30 mM [Petersen, Kappler, Szwergold and Brown (1992) Biochem. J. 284, 363-366]. The physiological significance of this process is still unknown. In the present study we report that the formation of fructose 3-phosphate from 50 mM fructose in intact erythrocytes is inhibited by 1-deoxy-1-morpholinofructose (DMF), a synthetic fructosamine, with an apparent K(i) of 100 microM. (31)P NMR analysis of cell extracts incubated with DMF indicated the presence of an additional phosphorylated compound, which was partially purified and shown to be DMF 3-phosphate by tandem MS. Radiolabelled DMF was phosphorylated by intact erythrocytes with an apparent K(m) ( approximately 100 microM) approx. 300-fold lower than the value reported for fructose phosphorylation on its third carbon. These results indicate that the physiological function of the enzyme that is able to convert fructose into fructose 3-phosphate in intact erythrocytes is probably to phosphorylate fructosamines. This suggests that fructosamines, which are produced non-enzymically from glucose and amino compounds, may be metabolized in human erythrocytes.