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Chapter 20 Somatostatin

1979; Elsevier BV; Linguagem: Inglês

10.1016/s0065-7743(08)61365-2

1557-8437

Daniel F. Veber, Richard Saperstein,

Glycosylation and Glycoproteins Research

This chapter explores the nature, biological evaluation of peptide hormone somatostatin, and also summarizes its effects on several organs. Somatostatin derives its name from its ability to inhibit the release of growth hormone from the pituitary. Somatostatin has been found to inhibit the secretion of various other hormones. It has been used as a valuable tool in the investigation of the relative role of glucagon in carbohydrate homeostasis and in diabetes mellitus. Withdrawal of insulin from juvenile diabetics, and subsequent infusion of somatostatin has been shown to result in the prevention of hypergluconemia, in revention of severe hyperglycemia, and in a rise in B-OH butyrate. Somatostatin also prevents the rise in glucose levels because of glucagon when alanine is administered parenterally. The fact that somatostatin effects nutrient absorption may play an important role in future ideas concerning the therapy. Somatostatin inhibits GH and thyrotropin releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) release from the pituitary. Somatostatin inhibits both the gastric secretion induced by gastrin and the release of gastrin that suggests a potential utility for the treatment of ulcers. Another important possible application is in the treatment of pancreatitis because somatostatin inhibits exocrine pancreatic secretion. The most widely studied properties of somatostatin analogs relate to the lowering of insulin, glucagon, growth hormone, and gastric secretion. The first approach undertaken toward increasing the duration of action of somatostatin analogs was through acylated somatostatin derivatives of reduced solubility. Another approach to increased metabolic stability can be through the introduction of conformational constraint. Another change in the nature of the ring of somatostatin through deletion of Asn-5 has shown selective lowering of insulin and growth hormone. The studies of analogs of somatostatin have shown substantial progress toward increased duration of action and improved biological specificity.