Pharmaceuticals & Vitamin D : Diabetes

Pharmaceuticals & Vitamin D Portfolios


Engineered Probiotics as Systemic Therapeutic Delivery Platform

UW–Madison researchers have developed bacteria engineered to systemically deliver a therapeutic polypeptide into a subject without the bacteria being substantially introduced into the bloodstream. This platform could be used to non-invasively increase systemic levels of hormones, peptides and potentially single-chain antibodies.

Using this new approach, the researchers engineered a lactic acid bacteria, Lactobacillus reuteri, to systemically deliver interleukin-22 (IL-22) in mice. The method is not limited to IL-22; other potential polypeptides include IL-35, insulin, leptin, a peptide inhibitor of PCSK9 and endolysin.

New Compounds for Treating High Blood Cholesterol and More

UW–Madison researchers have now developed a method using a rhodium-containing catalyst to make indole compounds, specifically cyclopropyl indoles and cyclohepta[b] indoles. The compounds may be developed into new pharmaceuticals to treat a variety of conditions.

Synthesizing Natural Products to Treat High Blood Cholesterol

UW–Madison researchers have developed an efficient method to synthesize indole compounds, specifically polysubstituted dimeric indoles. These compounds have potential health benefits because they are able to reduce the amount of PCSK9 in cells. PCSK9 is an enzyme known to play a major role in controlling the concentration of LDL cholesterol in the bloodstream.

Some of the compounds have been tested in vitro for their ability to increase the secretion of a potent blood sugar hormone in the body called glucagon-like peptide 1 (GLP-1). Others have the ability to selectively inhibit the secretion of interleukin-17 (IL-17), which is essential in many autoimmune diseases including arthritis, multiple sclerosis, psoriasis and inflammatory bowel disease.

The synthesis process involves a cascade reaction with transition metal catalysts. The resulting compounds can be further functionalized to yield more substituted indoles.

Non-Natural Peptides for Treating Diabetes

UW–Madison researchers have developed a new approach for designing GLP-1 receptor agonists that could be used to treat diabetes. The agonists retain GLP-1-like function but have prolonged activity in vivo.

The method includes strategically replacing native α-amino acid residues with conformationally constrained β-amino acid resides. The new α/β peptides mimic GLP-1 in terms of interacting with pancreatic beta cells and regulating blood glucose levels. The peptides are less susceptible to enzyme degradation due in part to the multiple β residue replacements.

Treating and Preventing Diabetes by Targeting EP3 Receptor

UW–Madison researchers have discovered an additional target for diabetic therapy. The gene, known as Ptger3, is over-expressed in diabetics. It encodes a receptor called EP3 that negatively impacts insulin secretion from beta cells. When that activity is suppressed, secretion can be elevated to healthy levels.

Their discovery may be used to develop a new pharmaceutical for boosting insulin secretion from beta cells. To do this, the pharmaceutical would work on two fronts to increase cAMP production. It would include a compound (like sitagliptin) that directly or indirectly activates AC, as well as a compound that blocks EP3 activity. Such an EP3-specific antagonist could be the commercially available agent L-798,106.

Vitamin D Analogs 2MD and 2AMD Prevent Type 1 Diabetes without Inducing Hypercalcemia

UW–Madison researchers have identified vitamin D analogs that can prevent type 1 diabetes in the NOD mouse at doses that do not induce hypercalcemia. The vitamin D compounds are 2α-methyl-19-nor-20(S)-1,25-dihydroxyvitamin D3, known as 2AMD, and 2-methylene-19-nor-20(S)-1,25-dihydroxyvitamin D3, known as 2MD.