PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice

• DOI: 10.1073/pnas.142298199
• Publication Date: 2002-09-30T16:42:53Z
• Authors: Bradley A. Zinker; Cristina M. Rondi...; James M. Trevillyan; Rebecca J. Gum; Jill E. Clampit; Jeffrey F. Waring; Nancy Xie; Denise Wilcox; Peer Jacobson; Leigh Frost; Paul E. Kroeger; Regina M. Reilly; Sandra Koterski; Terry J. Opgenorth; Roger G. Ulrich; Seth Crosby; Madeline Butler; Susan F. Murray; Robert A. McKay; Sanjay Bhanot; Brett P. Monia; Michael R. Jirousek
• Keywords: Hyperinsulinemia; Insulin receptor substrate; IRS2

The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide ob / and db mice. PTP1B treatment normalized plasma glucose levels, postprandial excursion, HbA 1C . Hyperinsulinemia also reduced with improved insulin sensitivity. protein mRNA were liver fat no effect skeletal muscle. Insulin signaling proteins, receptor substrate 2 phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, increased PI3-kinase p85α expression decreased fat. These changes correlated insulin-stimulated kinase B phosphorylation. gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase down-regulated. findings suggest that modulates fat, therapeutic modalities targeting inhibition may have clinical benefit type diabetes.