Subcutaneous Administration of Insulin is Associated With Regional Differences in Injection Depot Variability and Kinetics in The Rat

Background In humans, subcutaneous administration of insulin in the abdominal region or arm is associated with a faster absorption compared to the thigh or buttocks. We hypothesised that this is partly caused by differences in injection depot structure and kinetics and that the variability in insulin exposure differs between injection sites. Material and methods Regional effects on insulin pharmacokinetics were evaluated in a series of studies in Sprague Dawley rats dosed subcutaneously with insulin aspart in the neck or flank. Injection depots were visualised using µCT after subcutaneous dosing with insulin aspart mixed with the contrast agent iomeprol, and insulin exposure was determined between the scans by Luminescent Oxygen Channeling Immunoassay. Results Insulin absorption was significantly delayed by subcutaneous dosing in the flank compared to the neck region (p<0.01 or less). This delay was associated with smaller depots, as measured by reduced depot volume and surface area (p<0.001). Furthermore, the delayed absorption correlated with a slower depot disappearance (p<0.001). Regional differences in depot variability were not reflected by similar differences in pharmacokinetic variability. Conclusion Structure and kinetics of subcutaneous injection depots—as detected by µCT scans—predict insulin exposure and may thus contribute to the regional differences in insulin pharmacokinetics. The present methodology is applicable for visualisation of insulin injection depots in vivo. Our results did however not support a link between the variability in depot size and insulin pharmacokinetics.

Intraperitoneal insulin infusion: on the way to the artificial pancreas

Creating an "artificial pancreas" (a "closed loop" insulin pump, with self-adjusting insulin abilities, based on real time continuous glucose monitoring data) – is one of the most actual medical challenges of modern engineering and cybernetics.Artificial pancreas (AP) prototypes based on wearable insulin pump with subcutaneous insulin delivery are still problematic, mainly because of slow insulin pharmacokinetics. Intravenous insulin infusion via AP allows effectively maintain euglycaemia for inpatients, due to insulin pharmacokinetics and pharmacodynamics advantages. Unfortunately, it can’t be used for outpatients. Intraperitoneal insulin infusion is still relatively infrequently used in the world, but it is a promising alternative, compared to both previous methods due to a physiological action profile, fast insulin pharmacokinetics, relatively better safety and availability for outpatient usage.The purpose of this review is to describe the intraperitoneal insulin infusion features for diabetes patients at a point of AP creation perspectives.

Evaluation of the Association Metformin:Plantago ovataHusk in Diabetic Rabbits

In this experimental study we have investigated whether the inclusion of the dietary fiberPlantago ovatahusk could be recommended as coadjuvant in treatments with oral hypoglycemic drugs. We evaluated the use ofPlantago ovatahusk-metformin association in diabetic rabbits by determining its effects on glucose and insulin concentrations. Six groups of 6 rabbits were used. Groups 1 to 3 were fed with standard chow and groups 4 to 6 with chow supplemented withPlantago ovatahusk (3.5 mg/kg/day). Two groups (numbers 1 and 4) were used as controls (receiving standard or supplemented chow), two groups (numbers 2 and 5) received metformin orally, and the other two (numbers 3 and 6) were treated orally with metformin and psyllium. Plasma glucose concentrations were lower in groups fed with fiber-supplemented chow whereas insulin levels showed important interindividual variations. Glucose pharmacokinetics parameters showed significant differences inCmaxandtmaxin relation to fiber intake. Insulin pharmacokinetics parameters after treatment with oral metformin showed an important increase inCmax, AUC, andtmaxin animals fed with fiber. We conclude thatPlantago ovatahusk intake can contribute to the oral antihyperglycemic treatment of type 2 diabetes.