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Oral local delivery of therapeutic biologics is generally limited due to the multiple obstacles of the gastrointestinal (GI) tract, mainly represented by acidic stomach pH and digestive enzymes. In the present study, spray congealing was used to prepare solid lipid microparticles (SLMs) loaded with β-galactosidase (lactase), an enzyme used for the treatment of lactose intolerance, to achieve a local drug delivery to the small intestine. Lactase was characterized in terms of activity at different pH, kinetic parameters and proteolytic degradation by digestive enzymes. Then, five lipid excipients were used to prepare unloaded SLMs, which were tested regarding lipase-induced digestion. The lipid with the best performance (glyceryl trimyristate) was used to prepare lactase-loaded SLMs. Spray congealed SLMs were spherical with very good encapsulation efficiency (>95%). The ability of the SLMs to protect the enzyme from the degradation in gastric environment was correlated with the particle size and the best formulation preserved the lactase activity up to 70%. Lactase was promptly released in simulated intestinal environment, and an in vitro positive food effect was observed. The present study demonstrated the potential of spray congealing for the preparation of solid lipid formulations able to achieve local oral delivery of a biologic drug.

The aim of this study was to evaluate the fatty acid composition, lipolysis, lipid oxidation and volatile organic compounds (VOCs) in Colonnata lard from Large White (LW) or Cinta Senese (CS) pigs during one-year curing. CS lard contained a higher amounts of unsaturated fatty acids than LW one, due to the different rearing and feeding systems. Despite the higher lipolysis in CS backfat during the curing period, the rate of fatty acid and cholesterol oxidation was higher in LW. The amount of cholesterol oxidation products (COPs) and thiobarbituric acid reactive substances (TBARs) significantly decreased after 3 months of curing, regardless of the type of lard. VOCs composition of lard was affected by curing time, but not by breed. While volatile fatty acid oxidation products (mainly aldehydes) were present at the beginning of the curing time, subsequently other volatiles compounds (such as sulphur compounds and terpenes) that derived from ingredients used for lard production, increased in lard samples.

OBJECTIVE To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance. RESEARCH DESIGN AND METHODS The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m2, mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m2) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations. RESULTS In obese subjects, palmitate and glucose Ra in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose Ra was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate Ra (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate Ra and glucose Ra were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose Rd was greater in lean than obese subjects across the entire physiological range of plasma insulin. CONCLUSIONS Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.

The aim of the study was to investigate the acute effect of GH per se, independent from its lipolytic activity, on glucose and lipid oxidation and glucose turnover in seven healthy subjects. Five tests lasting 360 min were performed. Each test consisted of a 4-h equilibration period followed by a euglycemic hyperinsulinemic (25 mU/kg x h) clamp lasting 2 h. In test 1 (control experiment) saline was infused, leaving GH and FFA at basal levels. In tests 2, 3, and 4, GH was infused (80 ng/kg x min) to increase GH levels. Whereas in test 2 FFA levels were free to increase due to GH lipolytic activity, in test 3 FFA elevation was prevented by using an antilipolytic compound (Acipimox) that allowed evaluation of the effect of GH at low FFA levels. In test 4 (GH+Acipimox+heparin) GH infusion was associated with the administration of Acipimox and heparin to maintain FFA at the basal level to evaluate the effect of GH per se independent from GH lipolytic activity. In test 5 Acipimox and a variable heparin infusion were given to evaluate possible effects of Acipimox other than the inhibition of lipolysis. During the euglycemic hyperinsulinemic clamp in the presence of high GH and FFA levels (test 2), glucose oxidation was significantly lower and lipid oxidation was significantly higher than in tests 1, 3, 4, and 5. During the same period, hepatic glucose production was completely suppressed in the control study (test 1; 94%) and in test 5 (99.6%), whereas it was significantly less inhibited (65%, 74%, and 73%) when GH was administered in tests 2, 3, and 4. In conclusion, these results suggest that GH directly mediates the reduction of insulin's effect on the liver. In addition, the effect of GH on glucose and lipid oxidation is not direct, but is mediated by its lipolytic activity.