Short-term growth hormone excess is associated with impaired hepatic and extrahepatic responses to insulin in the absence of a change in insulin binding. To determine whether similar defects occur after chronic growth hormone excess, insulin dose-response curves for stimulation of glucose utilization and suppression of glucose production and monocyte and erythrocyte insulin binding were determined in five acromegalic patients and six healthy volunteers of comparable age, sex, and obesity. During infusion of insulin, glucose infusion rates required to maintain euglycemia were significantly lower (P less than 0.02 all) in the acromegalic patients than in the control subjects. Suppression of glucose production was impaired in the acromegalic subjects at insulin concentrations in the physiological range but not at insulin concentrations in the supraphysiological range. In contrast stimulation of glucose utilization was decreased in the acromegalic subjects at both physiological and supraphysiological insulin concentrations. Neither monocyte nor erythrocyte insulin binding differed significantly in the acromegalic and control subjects. These data indicate that chronic growth hormone excess is associated with a defect in both hepatic and extrahepatic insulin action. The decrease in glucose utilization at supraphysiological insulin concentrations in the acromegalic subjects and the normal monocyte and erythrocyte insulin binding suggest a postbinding alteration in insulin action.

No abstract

Our results suggest that, during infusion of omega-3 emulsions, EPA and DHA may enter cells as TG or partial glycerides within emulsion particles and not as FFA and that coinfusion of omega-3 emulsion with LCT emulsion at low omega-3:LCT emulsion ratios (up to 20% of total triglyceride as omega-3) will not substantially inhibit LCT hydrolysis.

Effective targeted drug delivery by cationic liposomes is difficult to achieve because of their rapid clearance from the blood circulation. Bolaamphiphiles that form monolayer membrane may provide vesicles with improved stability, as shown for archaeosomes. We investigated a series of bolaamphiphiles with acetylcholine head groups and systematic structural changes in their hydrophobic domain for their ability to form stable nanovesicles. Bolaamphiphiles with two aliphatic chains separated by a short amide midsection produced spherical nanovesicles ranging in diameter from 80 to 120 nm. These vesicles lost their encapsulated material within 24 hours of incubation in phosphate-buffered saline (PBS). Similar bolaamphiphiles with a longer midsection produced a mixture of fibers and more stable nanovesicles. Bolaamphiphiles with ester amide midsection produced only spherical nanovesicles that were stable during incubation in PBS for several days. Vesicles made from bolaamphiphiles with acetylcholine head groups conjugated to the aliphatic chain via the amine were less stable than vesicles made from bolaamphiphiles with head groups conjugated to the aliphatic chain via the acetyl group. Vesicles that were stable in vitro showed good stability in the blood circulation after intravenous administration to mice. These results help in elucidating the bolaamphiphile structures needed to form stable cationic vesicles for targeted drug delivery.

No abstract