Delayed insulin absorption correlates with alterations in subcutaneous depot kinetics in rats with diet-induced obesity.

OBJECTIVE: Obesity is associated with delayed insulin absorption upon subcutaneous (s.c.) dosing in humans. The aim of this study was to investigate whether alterations in depot structure and kinetics of the s.c. injection depot contribute to this delay. METHODS: Rats fed a high-fat diet (HFD) and low-fat diet (LFD) were included in a series of insulin pharmacokinetic and imaging studies. Injection depots were visualized with micro X-ray computed tomography imaging upon s.c. administration of insulin aspart mixed with the contrast agent iomeprol, and insulin aspart exposure was measured by means of luminescent oxygen channelling immunoassay. RESULTS: Body weight and fat mass were increased in rats fed an HFD vs. LFD (p < 0.05), whereas the lean mass was not. The HFD group exhibited delayed insulin absorption from the s.c. tissue (p < 0.001). This delay was associated with smaller injection depots upon s.c. dosing (p < 0.05) and correlated with a slower depot disappearance from the s.c. tissue (p < 0.05) compared with the LFD group. Depot disappearance from the s.c. tissue was inversely correlated with body fat mass (p < 0.05). CONCLUSIONS: Alterations in s.c. injection depot structure and kinetics may play a role in the obesity-associated delay in insulin absorption.

Factors Affecting the Absorption of Subcutaneously Administered Insulin: Effect on Variability.

Variability in the effect of subcutaneously administered insulin represents a major challenge in insulin therapy where precise dosing is required in order to achieve targeted glucose levels. Since this variability is largely influenced by the absorption of insulin, a deeper understanding of the factors affecting the absorption of insulin from the subcutaneous tissue is necessary in order to improve glycaemic control and the long-term prognosis in people with diabetes. These factors can be related to either the insulin preparation, the injection site/patient, or the injection technique. This review highlights the factors affecting insulin absorption with special attention on the physiological factors at the injection site. In addition, it also provides a detailed description of the insulin absorption process and the various modifications to this process that have been utilized by the different insulin preparations available.

Maternal intake of fish oil but not of linseed oil reduces the antibody response in neonatal mice.

Dietary levels of n-3 PUFA are believed to influence the immune system. The importance of the source of n-3 PUFA is debated. This study addressed how the content and source of n-3 PUFA in the maternal diet influenced tissue FA composition and the immune response to ovalbumin (OVA) in mice pups. From the day of conception and throughout lactation, dams were fed diets containing 4% fat from linseed oil (LSO), fish oil (FO) or a n-3 PUFA-deficient diet (DEF). Pups were injected with OVA within 24 h of birth and sacrificed at weaning (day 21). Overall, the content of n-3 PUFA in milk, liver and spleen reflected the source and only minor differences were observed in brain phospholipid 22:6n-3. The source had only limited influence on the n-3 PUFA accretion in peripheral tissue, with most pronounced differences in the spleen. The marine PUFA-group had reduced levels of total OVA-specific antibodies and OVA-IgG1 titers in the pup blood, while the response in the LSO-group did not differ from that in the DEF-group. There were no statistical differences in the cytokine responses to OVA-stimulated splenocytes, but the decrease in IgG1 was paralleled by an increase in IFNγ-production and a decrease in IL-6-production. Our results indicate that maternal intake of FO, but not of LSO, changes the offspring's antigen-specific response and potentially increases Th1-polarization.

Absorption by rats of tocopherols present in edible vegetable oils.

The absorption of tocopherols (alpha, gamma, and delta) and fatty acids from rapeseed (RO), soybean (SOO), and sunflower (SUO) oil, both from the natural oils and from the oils following moderate heating (180 degrees C for 15 min), was measured in lymph-cannulated rats. Oils were administered as emulsions through a gastrostomy tube, and lymph samples were collected for 24 h. The composition of tocopherols in oils and lymph fractions was measured by high-performance liquid chromatography, and fatty acids were measured by gas-liquid chromatography. The highest accumulated transport of alpha-tocopherol was observed after SUO administration, the lowest after SOO, with RO in between, corresponding to their relative contents (41.6 +/- 8.8, 32.7 +/- 5.0, and 24.9 +/- 4.3 microg at 24 h after administration of SUO, RO, and SOO, respectively). The calculated recoveries (in %) 24 h after oil administration were 21.4 +/- 4.5, 45.7 +/- 7.0, and 78.8 +/- 13.5 for SUO, RO, and SOO, respectively, suggesting that the absorption efficiency decreased when the alpha-tocopherol concentration increased. The recovery of alpha-tocopherol was higher than the recoveries of gamma- and delta-tocopherol, indicating that the different tocopherols were not absorbed to the same extent or with similar rates. No differences between unheated and heated oils were observed in the absorption of tocopherols, whereas heating led to lower absorption of fatty acids, thus showing no direct association between absorption of tocopherols and fatty acids.

Lymphatic transport in rats of several dietary fats differing in fatty acid profile and triacylglycerol structure.

We examined in rats the intestinal absorption of nine very different dietary fats (two rapeseed oils, corn, olive, palm and menhaden oil, butter, cocoa butter and lard) to investigate the influence of fatty acid profile and triacylglycerol structure on absorption. Absorption was followed for 24 h after administration of similar amounts of fats, and the accumulated lymphatic transport and amount of triacylglycerols found in lymph in response to the administered fats were calculated, revealing major differences. The transport of olive and low alpha-linolenic rapeseed oil was significantly higher than that of the other fats (P < 0.05), except corn oil. The lymphatic transport of the other fats followed a slower course, with cocoa butter and menhaden oil having the lowest amounts transported. The amount of triacylglycerols found in lymph in response to the administered fats at 8 h ranged from 27.5% of the administered dose for cocoa butter to 72.1% for olive oil. The value for cocoa butter was significantly lower than that for most other fats. At 24 h, the values ranged from 66.5% for cocoa butter to 121.2% for olive oil. The high value for olive oil suggested transport of endogenous as well as exogenous fatty acids. The low value observed after cocoa butter resulted from decreased lipolysis and possibly also low absorption of triacylglycerols with high levels of long-chain saturated fatty acids in the sn-1/3 position. Furthermore, a low value was observed after menhaden oil administration, suggesting decreased absorption of fats containing (n-3) long-chain polyunsaturated fatty acids. Overall, these results demonstrate the influence of the fatty acid composition and triacylglycerol structure on the lymphatic absorption of dietary fat.

Absorption in rats of rapeseed, soybean, and sunflower oils before and following moderate heating.

Rapeseed, soybean, and sunflower oil were heated for 15 min in a 5-mm oil layer in a pan at 180 degrees C. The fatty acid composition was almost unaffected by heating, while the polymer content rose slightly and the tocopherol content decreased, except in soybean oil. The absorption of oils before and after heating was investigated in lymph-cannulated rats. Oils were administered as emulsions through a gastrostomy tube and lymph was collected during the next 24 h. The highest accumulated lymphatic transport of total fatty acids was observed after administration of rapeseed oil, and the lowest after heated sunflower oil. The accumulated transport was similar for all unheated oils. The transport of fatty acids was significantly lower in rats receiving heated oil compared to those receiving the corresponding unheated oil. Small increases in polymers may have contributed to the decreased lymphatic transport of oil following heating, although this probably does not fully explain the effect. The absorption of sunflower oil was more affected by heating than the absorption of soybean or rapeseed oil. Furthermore, the largest decrease in total activity of tocopherols following heating was observed in sunflower oil. Overall, these results demonstrate that the absorption of vegetable oils is affected by moderate heating.

Lymphatic fatty acid absorption profile during 24 hours after administration of triglycerides to rats.

In this study we determined in rats the complete 24-h lymphatic fatty acid profile after administration of either rapeseed oil (RO) or rapeseed oil interesterified with 10:0 (RO/C10) with special emphasis on the transition from absorptive to postabsorptive phase. Rats were subjected to cannulation of the main mesenteric lymph duct and the next day oils were administered through a gastric feeding tube. Lymph was collected in 1-h fractions for the following 24 h. The time for maximum lymphatic transport of fatty acids was at 4 h with fast changes in fatty acid composition from the fatty acids of endogenous origin to those of the administered oils. Seven to eight hours after administration the transport was significantly lower than maximum, indicating the change from absorptive to postabsorptive phase. At 24 h after administration of either oil the transport of total fatty acids, palmitic acid (16:0), and linoleic acid (18:2n-6) together with oleic acid (18:1 n-9) after RO had not returned to the transport at baseline. In contrast, the transport of decanoic acid (10:0) and alpha-linolenic acid (18:3n-3) returned to baseline values between 12 and 15 h. This indicated that the absorption of purely exogenous fatty acids (illustrated by 10:0 and 18:3n-3) was complete at 15 h and that the fatty acids transported between 15 and 24 h were derived mostly from endogenous stores.