Speaking of LGND info, they have at least three presentations at the diabetes meeting this week on Rexinoids and TZDs. Here's one:
Abstract #:
0111
Abstract Type:
Orals
Abstract Category:
Islet Secretion, Sensitization and Senescence
Presentation Time:
4:15-6:15 PM
Presentation Date:
6/14/97
Activation of RXR with Rexinoids (RXR Selective Ligands) Function as Insulin Sensitizers in Type
II Diabetic Mice
DIANE L. CROMBIE 1,2, JAMES R. PATERNITI 1,2, RICHARD A. HEYMAN1,2, San Diego, CA, USA.
Receptors for retinoic acid (RAR), thyroid hormone (TR) and peroxisome proliferator activated receptors (PPARs)
preferentially bind to DNA to regulate transcription as heterodimers with the common partner, retinoid X receptor (RXR). This
raises the question whether rexinoids may replicate the activity of ligands for several of these receptors. We have identified a
series of synthetic RXR selecive ligands that are potent transcriptional activators of the RXRs. These RXR selective ligands,
function as RXR heterodimer selective agonists activating the RXR:PPARg dimer. Since PPARg is a target for antidiabetic
agents such as the thiazolidinediones, we investigated whether RXR ligands would alter insulin and glucose signaling. In mouse
models of non-insulin dependent diabetes mellitus (NIDDM) and obesity, including the ob/ob and db/db mice, RXR agonists
function as insulin sensitizers decreasing hyperglycemia, hypertriglyceridemia and hyperinsulinemia. Combination treatment with
the thiazolidinedione, BRL49653, further enhances the maximal response of either agent alone. When RXR agonists are used
during early stages of insulin resistance they block the progression of NIDDM. At late stages of insulin resistance, these agents
signficantly reduce the amount of exogenous insulin required to reduce the hyperglyemic state to the euglycemic levels. These
data suggest that activation of the RXR:PPARg heterodimer with rexinoids may provide a new therapeutic approach as
monotherapy or combination therapy for the treatment of insulin resistance.
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