Insulin sensitivity predicts glycemia after a protein load.

Protein ingestion results in small but distinct changes in plasma glucose and insulin. We hypothesized that the glycemic and/or insulin response to protein might be related to the degree of insulin sensitivity. Our aim was to determine the relationships between insulin sensitivity (assessed by euglycemic-hyperinsulinemic clamp) and postprandial glucose, insulin, C-peptide, and glucagon responses to a 75-g protein meal and a 75-g glucose load. Sixteen lean healthy Caucasian subjects (mean +/- SD age, 25 +/- 6 years; body mass index [BMI], 23.1 +/- 1.7 kg/m2) participated in the study. After the protein meal, the mean plasma glucose declined gradually below fasting levels to a nadir of -0.36 +/- 0.46 mmol/L from 60 to 120 minutes, showing wide intraindividual variation. Insulin sensitivity (M value) was 1.1 to 3.9 mmol/L/m2 min in the subjects and correlated inversely with the plasma glucose response to the protein meal (r = -.58, P = .03), ie, the most insulin-sensitive subjects showed the greatest decline in plasma glucose. In contrast, there was no correlation between insulin sensitivity and the insulin or glucagon response to the protein load, or between the M value and the metabolic responses (glucose, insulin, C-peptide, and glucagon) to the glucose load. Our study suggests that the net effect of insulin and glucagon secretion on postprandial glucose levels after a protein meal might depend on the individual's degree of insulin sensitivity. Gluconeogenesis in the liver may be less susceptible to inhibition by insulin in the more highly resistant subjects, thereby counteracting a decline in plasma glucose.

Single-stranded DNA oligoaptamers: molecular recognition and LPS antagonism are length- and secondary structure-dependent.

In Gram-negative bacterial infection, lipopolysaccharide (LPS) readily overwhelms the host innate immune system, which could result in inflammation and sepsis in severe cases. Therefore, developing anti-LPS molecules would confer an efficient antibacterial strategy. We used SELEX (Systemic Evolution of Ligands by EXponential enrichment) to isolate single-stranded DNA (ssDNA) aptamers. By immobilizing and exposing different orientations of the LPS molecule on hydrophobic and hydrophilic surfaces, two populations of aptamers were captured from a library of 10(14-15) ssDNA oligonucleotides. Progressive SELEX enriched the aptamers towards thymidine residues. The more hydrophobic aptamers with T-rich loops showed strong molecular recognition for the lipid A moiety of LPS, binding at affinity of up to K(D) of 10(-9)M, and eliciting 95% neutralization of endotoxicity. The longer ssDNAs exhibited greater avidity for LPS and conferred more efficacious antagonism against LPS. The nucleotide composition imposes subtle influence on the aptamer folding and affinity for LPS.