Solute carrier (SLC) transporters - a family of more than 300 membrane-bound proteins that facilitate the transport of a wide array of substrates across biological membranes - have important roles in physiological processes ranging from the cellular uptake of nutrients to the absorption of drugs and other xenobiotics. Several classes of marketed drugs target well-known SLC transporters, such as neurotransmitter transporters, and human genetic studies have provided powerful insight into the roles of more-recently characterized SLC transporters in both rare and common diseases, indicating a wealth of new therapeutic opportunities. This Review summarizes knowledge on the roles of SLC transporters in human disease, describes strategies to target such transporters, and highlights current and investigational drugs that modulate SLC transporters, as well as promising drug targets.

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SLC transporters as therapeutic targets: emerging opportunities

Crosslinking polyimides for membrane applications: A review

The copper(I)-catalyzed cycloaddition reaction between azides and alkynes has been employed to make metal-adhesive materials. Copper and brass surfaces supply the necessary catalytic Cu ions, and thus the polymerization process occurs selectively on these metals in the absence of added catalysts. Alternatively, copper compounds can be added to monomer mixtures and then introduced to reducing metal surfaces such as zinc to initiate polymerization. The resulting materials were found to possess comparable or superior adhesive strength to standard commercial glues, and structure-activity correlations have identified several important properties of the monomers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4392–4403, 2004

Click chemistry in materials synthesis. 1. Adhesive polymers from copper‐catalyzed azide‐alkyne cycloaddition

Glucocorticoids are steroid hormones that regulate multiple aspects of glucose homeostasis. Glucocorticoids promote gluconeogenesis in liver, whereas in skeletal muscle and white adipose tissue they decrease glucose uptake and utilization by antagonizing insulin response. Therefore, excess glucocorticoid exposure causes hyperglycemia and insulin resistance. Glucocorticoids also regulate glycogen metabolism. In liver, glucocorticoids increase glycogen storage, whereas in skeletal muscle they play a permissive role for catecholamine-induced glycogenolysis and/or inhibit insulin-stimulated glycogen synthesis. Moreover, glucocorticoids modulate the function of pancreatic α and β cells to regulate the secretion of glucagon and insulin, two hormones that play a pivotal role in the regulation of blood glucose levels. Overall, the major glucocorticoid effect on glucose homeostasis is to preserve plasma glucose for brain during stress, as transiently raising blood glucose is important to promote maximal brain function. In this chapter we will discuss the current understanding of the mechanisms underlying different aspects of glucocorticoid-regulated mammalian glucose homeostasis.

https://escholarship.org/content/qt9f7815hn/qt9f7815hn.pdf?t=qcdvp2

Regulation of Glucose Homeostasis by Glucocorticoids.

Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation)

Because of a huge amount of Zn2+ in secretory granules of pancreatic islet beta-cells, Zn2+ released in certain conditions might affect the function or survival of islet cells. We studied potential paracrine effects of endogenous Zn2+ on beta-cell death. Zn2+ induced insulinoma/islet cell death in a dose-dependent manner. Chelation of released endogenous Zn2+ by CaEDTA significantly decreased streptozotocin (STZ)-induced islet cell death in an in vitro culture system simulating in vivo circumstances but not in the conventional culture system. Zn2+ chelation in vivo by continuous CaEDTA infusion significantly decreased the incidence of diabetes after STZ administration. N-(6-methoxy-quinolyl)-para-toluene-sulfonamide staining revealed that Zn2+ was densely deposited in degenerating islet cells 24 h after STZ treatment, which was decreased by CaEDTA infusion. We show here that Zn2+ is not a passive element for insulin storage but an active participant in islet cell death in certain conditions, which in time might contribute to the development of diabetes in aged people.

https://diabetes.diabetesjournals.org/content/diabetes/49/3/367.full.pdf

Zinc as a paracrine effector in pancreatic islet cell death.

The alpha-glucosidase inhibitor 1-deoxynojirimycin (DNJ) is one of the simplest naturally occurring carbohydrate mimics, with promising biological activity in vivo. Although there is considerable interest in the pharmacological effects of DNJ, the antidiabetic effects of DNJ in type 2 diabetes mellitus have received little attention. In this work, DNJ was isolated from the silkworm (Bombyx mori), and its antidiabetic effects were evaluated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established animal model of human type 2 diabetes mellitus, and in control Long-Evans Tokushima Otsuka (LETO) rats. DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. Furthermore, there was significant loss of body weight in both groups. DNJ also showed significant antihyperglycemic effects in streptozotocin- and high-fat-diet-induced hyperglycemic rats. Its efficacy and dose profiles were better than those of acarbose, a typical alpha-glucosidase inhibitor in clinical use. Furthermore, a substantial fraction of DNJ was absorbed into the bloodstream within a few minutes of oral administration. DNJ was also detected in the urine. These findings suggest that its postprandial hypoglycemic effect in the gastrointestinal tract is a possible but insufficient mechanism of action underlying the antidiabetic effects of DNJ. Its antiobesity effect and improvement of insulin sensitivity are other possible antidiabetic effects of DNJ.

Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models.

The effects of dexamethasone on insulin release and biosynthesis are dependent on the dose and duration of treatment

A display apparatus having a casing in which an opening part is formed, includes: a liquid crystal display panel that is supported by the casing so that an image can be displayed through an opening part; a backlight unit that is provided behind the liquid crystal display panel and has a light source that emits light; a shield cover that is provided behind the backlight unit and is supported by at least one of the backlight unit and the casing; and a cooling fan unit that is combined to the shield cover and supplies cooling air to the backlight unit.

Seung-Hoon Oh

Papers

Zinc as a paracrine effector in pancreatic islet cell death.

Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models.

The effects of dexamethasone on insulin release and biosynthesis are dependent on the dose and duration of treatment

Cooling fan unit and display apparatus having the same

Adhesion improvement of epoxy resin/polyimide joints by amine treatment of polyimide surface