RESUMO
This review outlines the physiology of protein tyrosine phosphatase 1B (PTP1B) and its potential involvement in the states of insulin resistance that characterizes both obesity and type 2 diabetes. The primary focus of this review is upon the elucidation of the role and control of PTP1B enzyme activity in obesity and type 2 diabetes. Furthermore, since selectivity and cell permeability are the two most important requirements for the development of successful PTP1B inhibitors, recent progress in finding compounds meeting these criteria are discussed.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Animais , Fármacos Antiobesidade/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Insulina/fisiologia , Camundongos , Camundongos Knockout , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos Antissenso/uso terapêutico , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Especificidade por SubstratoRESUMO
Retinal pericytes are key cells involved in the regulation of retinal blood flow. The purpose of this work was to identify the K+ channel population expressed in cultured bovine retinal pericytes and to determine whether beta-adrenergic stimulation alters the activity of these channels. Isolated pericytes were obtained by homogenization and filtration of bovine retina and K+ channels were studied with the whole-cell configuration of the patch-clamp technique on 3-5 passaged pericytes. Pericytes expressed an inward current dependent on extracellular K+ concentration which was sensitive to micromolar concentrations of barium, a characteristic of an inward-rectifying K+ current. Furthermore, two voltage-dependent outward currents were also observed. Their activation and inactivation properties, as well as their respective sensitivity to 4-aminopyridine and iberiotoxin, were indicative of voltage-sensitive and large-conductance calcium-activated K+ channels (BKCa). Isoproterenol and dibutyryl cyclic adenosine monophosphate enhanced the activity of BKCa without affecting the other potassium currents. In conclusion, bovine retinal pericytes express mainly two outward potassium currents, KV and BKCa, as well as an inward rectifying K+ current, Kir. Physiologic stimuli such as an increase in extracellular potassium concentration or beta-adrenergic receptor stimulation enhance the activity of Kir and BKCa, respectively, suggesting a potential role for these channels in the control of retinal blood flow.