Glucose direct effects

In addition to the direct effects of hyperglycemia in enhancing the uptake of glucose into the liver, the hormone insulin plays a central role in regulating blood glucose. It is produced by the B cells of the islets of Langerhans in the pancreas in response to hyperglycemia. The B islet cells are freely permeable to glu-... 

Diabetic patients require more intense medical monitoring and selfmonitoring of blood glucose. Some anorectic agents have direct effects that improve glucose tolerance. 

Sometimes it is not possible to measure the direct effect of the drug. Endpoints or surrogate biomarkers are used to monitor the pharmacodynamics and pharmacokinetics of the drug. These markers may be changes in blood pressure, cholesterol level, concentrations of certain enzymes, proteins, blood glucose levels, and similar factors (see Table 6.2 for serum tumor markers and Appendix 7 for general biomarkers). 

A paper published six decades ago was the first to draw attention to the possibility that a change in the rate of transport of a molecule across the plasma membrane conld play a role in regulation of both intra- and extracellnlar metabolism that is, the regulation of the blood glncose level and the intracellular metabolism of glucose. The paper was entitlied A hypothesis of insulin action is proposed which attributes to insulin the role of facilitating the rate of transport of some hexoses into the cell as opposed to a direct effect on intracellular metabolism (Levine et al. 1950). 

There are numerous substances that are administered intravenously and have a direct effect on biochemical analysis. Obviously, glucose or electrolyte concentrations will be spuriously elevated if the specimen is taken from the same vein into which these substances are being administered. The presence of sulfobromophthalein dye (BSP) in serum or plasma will interfere with protein determined by the biuret method. The... 

The high degree of stereoselectivity claimed is surprising. In the system used, no directive effects causing exclusive reaction of the C-4 hydroxyl group of D-glucose are apparent. Indeed, in an independent study using this... 

The level of infection in a host has a direct effect on the carbohydrate content of cestodes (796) and has been shown by Henderson (317) to affect glucose absorption by H. diminuta in vitro (Fig. 5.1). These are manifestations of the crowding effect, reported in Raillietina, H. microstoma, H. nana and, most notably, H. diminuta (697), which results in an inverse correlation between worm size and increasing population density. Competition for host dietary carbohydrate presumably plays a role in the crowding effect, but the phenomenon is complex and a number of other factors are probably involved (348, 697, 979, 980). This phenomenon is addressed further in Chapter 9. 

EN28 Glick, M.R., Ryder, K.W. and Pemberton, M.B. (1991). Evaluation of the Lily/Elco Direct 30/30 and other blood glucose monitoring devices by comparison with Kodak Ektachem 700 glucose results Effects of interferences. Clin. Chem. 37, 932, Abstr. 108. 

Diagrammatic representation of insulin secretion from pancreatic fi cells. The sequence of events of insulin secretion coupled to glucose entry into fi cells consists of glucokinase action, ATP production, inhibition of the ATP-sensitive K+ channel, membrane depolarization, Ca + influx, and insulin release. Neurotransmitters acetylcholine and norepinephrine stimulate and inhibit insulin secretion via trimeric G-proteins Gq and Gj, respectively. Glucagon-like peptide (GLP) promotes insulin release via the G-protein G. Sulfonamides and diazoxide have direct effects on sulfonylurea receptors (SURs) the former promotes insulin release and the latter inhibits insulin release. +, Stimulation —, inhibition. Other abbreviations are given in the text. 

Medication can be delivered via the eye in the form of eyedrops or in an ocular device. Sodium or zinc insulin was incorporated into a Gelfoam sponge-based device. An in vitro dissolution test indicated that the release of insulin from the device was proportional to the flow rate of the dissolution medium. An in vivo dissolution experiment provided support for the hypothesis that there was a direct relationship between the prolonged pharmacological response to insulin and its release from the device. The ocular device with or without the aid of an enhancer was placed in the eye of rabbits as an ocular insert and produced a uniform blood glucose-lowering effect of 60% over 8h. The blood glucose... 

---