Significance Tyrosine kinases which phosphorylate tyrosine residues in signaling proteins are involved in transduction of insulin's actions after it binds to insulin receptors. People and animals with Type 2 diabetes are resistant to the actions of insulin. One approach to treating Type 2 diabetes is to enhance the insulin signal by inhibiting the enzymes which are involved in dephosphorylating tyrosine (Tyrosine phosphatases) which inactivates the signal. In order to identify potential tyrosine phosphatase targets for drugs that will inhibit the activity of these enzymes the specific phosphatases functioning in primates need to be identified. Primate tyrosine phosphatases have not previously been cloned. Objectives To obtain insulin sensitive tissues (fat, muscle, and liver) for polymerase chain reaction (PCR) cloning of tyrosine phosphatases. Cloning was performed by and at Sugen, Inc. Results Tissues were collected at the California Regional Primate Research Center (CRPRC). Samples were obtained from 5 normal weight and 5 obese adult male rhesus. Fat (0.5 g) and muscle (0.5 g) samples was collected by surgical biopsy under ketamine anesthesia. Liver samples (20-50 mg) were collected by ultrasound-guided needle biopsy under ketamine anesthesia. Biopsy procedures were performed by CRPRC veterinarians. Samples were placed in sterile plastic vials and immediately frozen in liquid nitrogen. The frozen tissue samples were shipped on dry ice to Sugen, Inc. in Redwood City, CA. Sugen has cloned several tyrosine phosphatases from the samples. Tissue samples have also been obtained under this project/protocol for gene array analysis by our laboratory. Future Directions No further experiments are planned at this time, however, it is possible that in the future we will want to obtain additional tissues from these or other animals for similar experiments. KEY WORDS tyrosine phosphatases, obesity, diabetes, PCR cloning, muscle, Adipose, liver FUNDING Sugen, Inc., Redwood City, CA
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