Compositions and methods for inhibiting the enzymatic activity of PTP-1B

A method of identifying inhibitors of the enzymatic activity of the PTP-1B protein comprising:

• (a) transfecting a cell with DNA encoding the human PTP-1B protein;
• (b) culturing the cells of step (a) under conditions such that PTP-1B protein is produced;
• (c) measuring the enzymatic activity of the PTP-1B protein in the presence and in the absence of a substance suspected of being an inhibitor of the enzymatic activity of the PTP-1B protein;
• where a decrease in the enzymatic activity of the PTP-1B protein in the presence as compared to the absence of the substance indicates that the substance is an inhibitor of the enzymatic activity of the PTP-1B protein.

A method of determining whether a substance modulates glucose or triglyceride levels in a mammal that comprises:

• (a) providing an enzymatically active preparation of PTP-1B;
• (b) measuring the enzymatic activity of PTP-1B in the enzymatically active preparation of PTP-1B in the presence and in the absence of a substance suspected of being an inhibitor of the enzymatic activity of PTP-LB, thus identifying a substance that is an inhibitor of the enzymatic activity of PTP-1B;
• where a decrease in the enzymatic activity of PTP-1B in the presence as compared to the absence of the substance indicates that the substance is an inhibitor of the enzymatic activity of PTP-1B;
• (c) administering the substance that is an inhibitor of the enzymatic activity of PTP-1B to a mammal;
• (d) measuring the blood glucose level or triglyceride levels of the mammal in step (c) and comparing the blood glucose level or triglyceride levels of the mammal in step (c) with the blood glucose level or triglyceride levels of a mammal that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B;
• where a difference in the blood glucose level or triglyceride levels of the mammal in step (c) as compared with the blood glucose level or triglyceride levels of the mammal that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B indicates that the substance modulates glucose or triglyceride levels in a mammal.

A method of determining whether a substance regulates obesity in a mammal that comprises:

• (a) providing an enzymatically active preparation of PTP-1B;
• (b) measuring the enzymatic activity of PTP-1B in the enzymatically active preparation of PTP-1B in the presence and in the absence of a substance suspected of being an inhibitor of the enzymatic activity of PTP-1B, thus identifying a substance that is an inhibitor of the enzymatic activity of PTP-1B;
• where a decrease in the enzymatic activity of PTP-1B in the presence as compared to the absence of the substance indicates that the substance is an inhibitor of the enzymatic activity of PTP-1B;
• (c) administering the substance that is an inhibitor of the enzymatic activity of PTP-1B to a mammal;
• (d) measuring the weight gain of the mammal in step (c) when the mammal of step (c) is fed a high fat, high carbohydrate diet and comparing the weight gain of the mammal in step (c) with the weight gain of a mammal fed a high fat, high carbohydrate diet that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B;
• where a difference in the weight gain of the mammal in step (c) as compared with the weight gain of the mammal that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B indicates that the substance regulates obesity in a mammal.

A method of determining whether a substance modulates glucose or triglyceride levels in a mammal that comprises:

• (a) transfecting a cell with DNA encoding the human PTP-1B protein;
• (b) culturing the cells of step (a) under conditions such that PTP-1B protein is produced;
• (c) measuring the enzymatic activity of the PTP-1B protein in the transfected cells in the presence and in the absence of a substance suspected of being an inhibitor of the enzymatic activity of the PTP-1B protein;
• where a decrease in the enzymatic activity of the PTP-1B protein in the presence as compared to the absence of the substance indicates that the substance is an inhibitor of the enzymatic activity of the PTP-1B protein;
• (d) administering the substance that is an inhibitor of the enzymatic activity of PTP-1B to a mammal;
• (e) measuring the blood glucose level or triglyceride levels of the mammal in step (d) and comparing the blood glucose level or triglyceride levels of the mammal in step (d) with the blood glucose level or triglyceride levels of a mammal that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B;
• where a difference in the blood glucose level or triglyceride levels of the mammal in step (d) as compared with the blood glucose level or triglyceride levels of the mammal that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B indicates that the substance modulates glucose or triglyceride levels in a mammal.

A method of determining whether a substance regulates obesity in a mammal that comprises:

• (a) transfecting a cell with DNA encoding the human PTP-1B protein;
• (b) culturing the cells of step (a) under conditions such that PTP-1B protein is produced;
• (c) measuring the enzymatic activity of the PTP-1B protein in the transfected cells in the presence and in the absence of a substance suspected of being an inhibitor of the enzymatic activity of the PTP-1B protein;
• where a decrease in the enzymatic activity of the PTP-1B protein in the presence as compared to the absence of the substance indicates that the substance is an inhibitor of the enzymatic activity of the PTP-1B protein;
• (d) administering the substance that is an inhibitor of the enzymatic activity of PTP-1B to a mammal;
• (e) measuring the weight gain of the mammal in step (d) when the mammal of step (d) is fed a high fat, high carbohydrate diet and comparing the weight gain of the mammal in step (d) with the weight gain of a mammal fed a high fat, high carbohydrate diet that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B;
• where a difference in the weight gain of the mammal in step (d) as compared with the weight gain of the mammal that has not been administered the substance that is an inhibitor of the enzymatic activity of PTP-1B indicates that the substance regulates obesity in a mammal.