Unmasking of proteinuria in the course of genetic dissection of nonproteinuric diabetic nephropathy.

We previously described the development of nonproteinuric diabetic nephropathy (NPDN) in the Cohen diabetic rat (CDs), a model that simulates Type 2 diabetes in humans. Using linkage analysis in an F2 cross, we currently set out to investigate the mechanisms underlying NPDN. We crossbred between CDs and SBN/y, a nondiabetic rat strain, generated F1 and F2 progenies, fed them diabetogenic diet that elicits diabetes and NPDN in CDs but not in SBN/y, and determined metabolic and renal phenotypes.

Ion-channel reconstitution.

In this chapter, a detailed protocol is given for ion-channel reconstitution in the two most used model membranes: planar bilayers and liposomes. In the planar bilayer section, methods are described for the expression of ion channels in Xenopus laevis oocytes, the isolation of their membranes, the insertion of ion channels into the bilayer by vesicle fusion, and the recording of single-ion channel current measurements at a constant applied voltage. The reconstitution of bacterial channels in liposomes is also given.

Effect of lercanidipine on kidney microanatomy in Cohen-Rosenthal diabetic hypertensive rats.

The study was undertaken to determine the effect of treatment with the dihydropyridine-type calcium antagonist lercanidipine on the renal vasculature in Cohen-Rosenthal diabetic hypertensive rats, a genetic model of hypertension associated with type 2 diabetes mellitus. Eight animals were given a daily oral dose of 3 mg/kg lercanidipine in drinking water for 8 weeks, and 6 control animals received no treatment. The effects on blood pressure, glucose level, and kidney microanatomy were evaluated.

Dissection of the components for PIP2 activation and thermosensation in TRP channels.

Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in the activation of several transient receptor potential (TRP) channels. The role of PIP2 on temperature gating of thermoTRP channels has not been explored in detail, and the process of temperature activation is largely unexplained. In this work, we have exchanged different segments of the C-terminal region between cold-sensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the role of the segment in PIP2 and temperature activation.

A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels.

Temperature transduction in mammals is possible because of the presence of a set of temperature-dependent transient receptor potential (TRP) channels in dorsal root ganglia neurons and skin cells. Six thermo-TRP channels, all characterized by their unusually high temperature sensitivity (Q10 > 10), have been cloned: TRPV1-4 are heat activated, whereas TRPM8 and TRPA1 are activated by cold. Because of the lack of structural information, the molecular basis for regulation by temperature remains unknown.