Type I diabetes is very manageable by taking daily doses of exogenous insulin. However, researchers of the University of South Dakota pulled together a method utilizing G-protein coupled receptor 119 (GPR119) and dipeptidylpeptidase-IV (DPP-IV) to regenerate lost ß-islet cells of diabetics and restore insulin production in the body.
ß-cells are the insulin generators of the body, but in type I diabetes patients, they don’t exist or don’t work. GPR119, when activated by an agonist such as PSN632408, stimulates ß-cell replication, increases GLP-1 secretion, reduces food intake, and decreases body weight gain. If hyperstimulated in type I diabetes sufferers the level of insulin reached would be closer to that of normal body levels, which is why this was a target of this study. Contrarily, DPP-IV works to degrade or breakdown GLP-1, which is a protein that stimulates insulin release from ß-cells, enhances ß-cell proliferation, and prevents ß-cell programmed cell death.
In the study, diabetic mice with blood glucose levels of 400 to 500 mg/dL were treated with PSN632408 and/or sitagliptin for 7 weeks. The former acted as a GPR119 agonist and the latter as a DPP-IV inhibitor. After treatment ended, the three different treatment groups obtained the following percentages of normoglycemia (blood glucose < 200 mg/dL) mice:
– PSN632408, 32% mice with normoglycemia
– Sitagliptin, 36% mice with normoglycemia
– PSN632408 & sitagliptin, 59% mice with normoglycemia
The average drop in blood glucose was 257 mg/dL after seven weeks. The treatment actively reversed type I diabetes in these mice.
Further tests showed increased levels of GLP-1 (7.6±0.4 pmol/L in control mice, 14.8±1.0, 35.9±8.6, 44.2±10.5 pmol/L in mice treated with PSN632408, Sitagliptin, or both respectively), ß-cell replication, and ß-cell regeneration.
Mice treated with a GRP119 agonist and DPP-IV inhibitor showed increased ß-cell regeneration and overall insulin production. As mice have similar GRP119/DPP-IV pathways to humans, these results are very exciting for the diabetes scene.
Drinking (or painfully auto-injecting) daily insulin may no longer be necessary for diabetics if the GRP119 agonist/DPP-IV inhibitor treatment is approved for clinical use.
Ansarullah, Yan Lu, Martha Holstein, Brittany DeRuyter, Alex Rabinovitch, Zhiguang Guo. Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor. PLoS ONE, 2013. http://dx.doi.org/10.1371/journal.pone.0053345