Insulin absorption

Absorbance measurements, pyridinium ion with CN- in micro-emulsions, 177 Absorption insulin... 

Recent development of insulin analogues has altered the rates of absorption. Insulin with aspartate and glutamate substituted at positions B9 and B27 respectively crystallizes poorly and has been termed "monomeric insulin (Vora et al., 1988). This insulin is absorbed more rapidly from subcutaneous depots and thus may be useful in meeting postprandial demands. In contrast, other insulin analogues tend to crystallize at the site of injection and are absorbed more slowly (Markussen et al., 1988). Insulins with enhanced biological potency have been produced by substitution of aspartate for histidine at position BIO and by modification of the C-terminal residues of the B-chain (Schwartz et al., 1989). 

Ellis, P.R., Rayment, P. and Wang, Q. 1996. A physico-chemical perspective of plant polysaccharides in relation to glucose absorption, insulin secretion and the entero-insular axis, Proc. Nutr. Soc., 55 881-898. 

NPH Isophane Human Insulin Suspension. NPH isophane insulin, also called Humulin N, Insulatard NPH Human, or Novolin N is an intermediate-acting form of human insulin produced by recombinant DNA techniques. Mixtures Humulin 70/30 and Novolin 70/30 contain 70% NPH isophane and 30% regular, whereas Humulin 50/50 contains 50% NPH isophane and 50% regular. It is adrninistered subcutaneously and should not be given intravenously. Absorption is delayed because the insulin is conjugated with protamine in a complex of reduced isoelectric solubiUty. Therapeutically, this preparation is probably comparable to purified porcine NPH insulin. However, human NPH insulin may have a slightly shorter duration of action than comparable purified porcine products. 

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

Blood Glucose and Insulin Response. In humans, ingestion of sugar alcohols has shown a significantly reduced rise in blood glucose and insulin response, owing to slow absorption by the body. As a result, many foods based on sugar alcohols have been used safely in the diets of diabetics (208). 

Permeation enhancers are used to improve absorption through the gastric mucosa. Eor example, oral dehvery of insulin (mol wt = 6000) has been reported from a water-in-oH- emulsion containing lecithin, nonesterified fatty acids, cholesterol [57-88-5], and the protease inhibitor aprotinin [9087-70-1] (23). 

SLTR1/Kir6.2 Glibenclamide and glipizide that block pancreatic KAXP channels have been used for the treatment of type II diabetes. New class of insulin secretagogues includes repaglinide and nateglinide, which improve insulin secretion, action and reduce carbohydrate absorption. 

The effects of metoclopramide are antagonized by concurrent administration of anticholinergics or narcotic analgesics. Metoclopramide may decrease the absorption of digoxin and cimetidine and increase absorption of acetaminophen, tetracyclines, and levodopa Metoclopramide may alter die body s insulin requirements. 

Under normal feeding patterns the rate of tissue protein catabolism is more or less constant throughout the day it is only in cachexia that there is an increased rate of protein catabolism. There is net protein catabolism in the postabsorptive phase of the feeding cycle and net protein synthesis in the absorptive phase, when the rate of synthesis increases by about 20-25%. The increased rate of protein synthesis is, again, a response to insulin action. Protein synthesis is an energy-expensive process, accounting for up to almost 20% of energy expenditure in the fed state, when there is an ample supply of amino acids from the diet, but under 9% in the starved state. 

Diabetic patients have reduced antioxidant defences and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. EC has a pronounced insulin-like effect on erythrocyte membrane-bound acetylcholinesterase in type II diabetic patients (Rizvi and Zaid, 2001). Tea polyphenols were shown to possess anti-diabetic activity and to be effective both in the prevention and treatment of diabetes (Choi et al, 1998 Yang et al, 1999). The main mechanism by which tea polyphenols appear to lower serum glucose levels is via the inhibition of the activity of the starch digesting enzyme, amylase. Tea inhibits both salivary and intestinal amylase, so that starch is broken down more slowly and the rise in serum glucose is thus reduced. In addition, tea may affect the intestinal absorption of glucose. 

VAUGELADE P, HOEBLER C, BERNARD F, GUILLON F, LAHAYE M, DUEE P H, DARCY-VRILLON B (2000) Non-Starch polysaccharides extracted from seaweed can modulate intestinal absorption of glucose and insulin response in the pig. Reprod Nutr Dev. 40 33-47. 

Increased peripheral utilization of glucose, increased insulin receptors and improved glucose absorption. (Hikino et al., 1988 Hikino and Hayashi et al., 1989 Masayoshi, 1987). 

Regular insulin is unmodified crystalline insulin commonly referred to as natural insulin. It is a clear solution that has a relatively rapid onset and short duration of action. On subcutaneous injection, regular insulin forms small aggregates called hexamers that undergo conversion to dimers followed by monomers before systemic absorption can occur. Therefore, patients should be counseled to inject regular insulin subcutaneously 30 minutes prior to consuming a meal. Regular insulin is the only insulin that can be administered intravenously. 

Insulin pump therapy consists of a programmable infusion device that allows for basal infusion of insulin 24 hours daily, as well as bolus administration following meals. As seen in Fig. 40-3, an insulin pump consists of a programmable infusion device with an insulin reservoir. This pump is attached to an infusion set with a small needle that is inserted in subcutaneous tissue in the patient s abdomen, thigh, or arm. Most patients prefer insertion in abdominal tissue because this site provides optimal insulin absorption. Patients should avoid insertion sites along belt lines or in other areas where clothing may cause undue irritation. Infusion sets should be changed every 2 to 3 days to reduce the possibility of infection. 

Normal Rabbits. Six male, white rabbits (2.5 - 3.0 kg) were housed individually. Animals were fasted overnight for 16 hours (with access to water) prior to each experiment to reduce the gastrointestinal content and absorption variability. After treatment with either a control dose or experimental insulin in poly(acrylic acid) resin dose, a one week washout period was required before the next experiment. The protocol called for blood samples to be taken from an indwelling ear catheter at -1, -.5, -.25, +.5, +1, +1.5, +2, +3, +4, +5 and +6 hours. Serum glucose levels were determined by an oxidase colorimetric method using the Sigma 510 Glucose Kit. 

When diabetic rabbits (24) were treated with 50 IU of bovine insulin imbibed at 50 mg/g poly (acrylic acid) (Figure 14) no reduction in serum glucose over that achieved by the dry blend control could be detected. Pretreatment of the animals with oral doses of either a penetration enhancer, sodium taurocholate, or a protease inhibitor, aproteinin, failed to improve the insulin activity. One possible explanation for this unexpected lack of activity might be that the diseased animals exhibit impaired ileal absorption of fluids (25). 

The results obtained from A-II injected animals (Figure 15) confirmed that the peak arterial pressure response is a reliable indirect indicator of A-II absorption (27,25). On this basis it is very unlikely that oral administration of A- II-impregnated resin (Figure 16) resulted in any significant absorption, even at an A-II dose which was 25X higher than the maximally effective subcutaneous dose. As in the insulin studies, the detectable response was observed about two and one-half hours after dosing. 

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