Food derived carbonyl compounds affect basal and stimulated secretion of interleukin-6 and -8 in Caco-2 cells.

BACKGROUND: The carbonyl compounds methylglyoxal (MG) and glyoxal (G) are reactive intermediates generated in a variety of foods and beverages during processing and prolonged storage. AIM AND METHODS: We investigated direct effects of these compounds on intestinal cells determining the basal and stimulated secretion of IL-8 and IL-6 in vitro. RESULTS: MG or G induced a concentration dependent enhancement of IL-8 and IL-6 secretion compared to baseline levels. A co-incubation with pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) or lipopolysaccharides (LPS) and increasing MG concentrations further enhanced IL-8 and IL-6 secretion. For G, however, this additive effect was only observed in TNF-alpha and IL-1beta treated cells, but not after co-incubation with LPS. CONCLUSION: These results suggest a pro-inflammatory effect of G and MG at high concentrations in human intestinal cells by stimulating IL-8 and IL-6 cytokine levels. Effects of G and MG in combination with other cytokines may negatively affect inflammatory processes.

Nocturnal glucose metabolism after bedtime injection of insulin glargine or neutral protamine hagedorn insulin in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Insulin glargine is a long-acting human insulin analog often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycemic events compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning. METHODS: In 10 type 2 diabetic patients, euglycemic clamps were performed, including [6,6'](2)H(2) glucose, to study the rate of disappearance (Rd) and endogenous production (EGP) of glucose during the night. On separate days at bedtime (2200 h), patients received a sc injection of insulin glargine, NPH insulin, or saline in a randomized, double-blind fashion. RESULTS: Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared with insulin glargine. By contrast, in the morning, insulin glargine was more effective, increasing Rd by 5.8 micromol/kg(-1).min(-1) (95% confidence interval 4.7-6.9) and reducing EGP -5.7 (-5.0 to -6.4) compared with NPH insulin. Nearly 80% of the glucose lowering effect in the morning was due to insulin glargine's reduction of EGP. Its injection was associated with one-third lower morning glucagon levels compared with NPH insulin (P = 0.021). CONCLUSION/INTERPRETATION: Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin.