Methods for identifying compounds for treating diabetes mellitus

Abstract

The invention is directed to methods for identifying candidate beta cell-sensitizing compounds comprising providing a pancreatic beta islet cell population derived from a diabetic subject, contacting the beta islet cell population with one or more somatostatin receptor 5-binding compounds, and identifying those somatostatin receptor 5-binding compounds that promote insulin secretion from the pancreatic beta islet cell population at a higher rate than from a control cell population. The invention is further directed to methods for treating type II diabetes comprising administering a beta cell-sensitizing compound identified by the first method of the invention to a diabetic patient in need of treatment.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims priority from the co-pending provisional application Ser. No. 60 / 569,834 filed May 10, 2004, incorporated by reference herein in its entirety.BACKGROUND OF THE INVENTION [0002] Diabetes mellitus is a complex chronic disorder that results primarily either from partial or complete lack of insulin secretion by the pancreas. The endocrine pancreas consists of the islets of Langerhans, which include several different cell types, including beta cells that are responsible for insulin secretion, alpha cells that produce glucagon, and delta cells that produce somatostatin (Luft, Efendic et al. Med Biol 52:428-430, 1974). Insulin and glucagon secreted from the beta and alpha cells serve to regulate blood glucose levels. [0003] In diabetic patients, the pancreas produces insufficient or no insulin, the hormone which is responsible for the uptake of glucose into cells. As a result, the level of glucose in the blood becomes ab...

AI Technical Summary

Benefits of technology

[0012] The inventors of the present invention have unexpectedly found that SSTR5-selective antagonists selectively promote insulin secretion at elevated glucose levels in pancreatic islets isolated from Type II diabetic rats to a greater degree than they promote insulin release from these pancreatic islets isolated from normoglycemic animals. Thus, SSTR5-selective antagonists can act as “beta-cell sensitizers” and be used, for example, to promote glucose-induced insulin release in diabetic subjects while minimizing hypoglycemic episodes caused by indiscriminate promotion of insulin secretion regardless of glucose concentration.

Problems solved by technology

As a result, the level of glucose in the blood becomes abnormally high.

In patients with Type II diabetes, insufficient insulin is produced to maintain normal blood glucose levels.

Often the body is resistant to the effects of insulin as the transduction of insulin signal is impaired.

If the diabetes is poorly controlled it can lead to diabetic complications.

Intensive insulin treatment or treatments that produce insulin, such as sulfonylureas and glinides, increase the risk of hypoglycemia (or insulin shock), which occurs if blood glucose levels fall below normal.

To date, FDA approved drugs that promote insulin secretion do so indiscriminately, at both high and low blood glucose levels, which can lead to hypoglycemia, discouraging the use of such drugs.

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