Inhibition of SMAD-Signaling Leads to Enhanced Insulin Production and Better Glucose Control: A Potential Therapy for Diabetes and Associated Complications Due to Hyperglycemia
Description of Invention:
TGFbeta and related proteins, activins and bone morphogenetic proteins (BMPs), are critical during pancreas development. Alterations in the TGFbeta pathway are observed in diseases of the pancreas, including diabetes and cancer, although the precise ramifications of altered TGFbeta functions are unclear. The DPC4 (deleted in pancreas cancer 4) locus that encodes the TGFbeta-signaling intermediate, SMAD 4, is mutated in 55-70% of pancreatic cancers and alterations in expression of the TGFbeta receptors I and II (TbetaRI and TbetaRII) are also observed during pancreatic cancer progression. These observations are consistent with an integral role of the TGFbeta pathway components in pancreas biology and disease progression. However, the molecular details and the target cell population of TGFbeta signals during pancreas development and disease are not known.
SMAD proteins are downstream mediators of signals from TGFbeta 1,2,3 and activin, and SMAD proteins have been implicated as important factors in cellular proliferation, differentiation and migration. This invention identifies another important regulatory role for the TGFbeta-signaling pathway in insulin production. The inventors have shown that low levels of TGFbeta can suppress insulin production through the actions of the SMAD signaling proteins. Small molecule regulators of SMAD-dependent signaling may lead to better insulin production and allow better glucose regulation. Thus, controlled administration of TGFbeta signaling regulators may be useful in the treatment of diabetes, hyperglycemia and related complications.
Inventors:
Sushil G. Rane et al. (NCI)
Patent Status:
DHHS Reference No. E-235-2004/0 Licensing Status: This technology is no longer available for licensing.
For Additional Information Please Contact: Tara L. Kirby Ph.D.
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