Novel therapeutic strategies for the treatment of Type 2 diabetes

Abstract

Diabetes mellitus is the most common endocrine disease, accounting for over 200 million people affected worldwide. It is characterized by a lack of insulin secretion and/or increased cellular resistance to insulin, resulting in hyperglycemia and other metabolic disturbances. People with diabetes suffer from increased morbidity and premature mortality related to cardiovascular, microvascular and neuropathic complications. The Diabetes Control and Complication Trial (DCCT) has convincingly demonstrated the relationship of hyperglycemia to the development and progression of complications and showed that improved glycemic control reduced these complications. Although the DCCT exclusively studied patients with Type 1 diabetes, there is ample evidence to support the belief that the same relationship between metabolic control and clinical outcome exists in patients with Type 2 diabetes. Therefore, a major effort should be made to develop and implement more effective treatment regimes. This article reviews those novel drugs that have been recently introduced for the management of Type 2 diabetes, or that have reached an advanced level of study and will soon be proposed for preliminary clinical trials. They include: (i) compounds that promote the synthesis/secretion of insulin by the beta-cell; (ii) inhibitors of the alpha-glucosidase activity of the small intestine; (iii) substances that enhance the action of insulin at the level of the target tissues; and (iv) inhibitors of free fatty acid oxidation.

Inhibition of α-amylase activity by condensed tannins

“…Their inhibition leads to a decrease in the blood glucose level since monosaccharides are the forms of carbohydrates that are readily absorbed in the small intestine (Funke & Melzig, 2006). It has been shown that an improved glycaemic control reduces diabetes related complications (Perfetti, Barnett, Mathur, & Egan, 1998).…”

Traditionally used plants in diabetes therapy: phytotherapeutics as inhibitors of alpha-amylase activity

“…Many and diverse therapeutic strategies for the treatment of Type 2 diabetes are known. Conventional treatments include the reduction of the demand for insulin, stimulation of endogenous insulin secretion, enhancement of the action of insulin at the target tissues and the inhibition of degradation of oligo-and disaccharides (Groop et al 1997, Perfetti et al 1998. One group of drugs introduced in the management of Type 2 diabetes is represented by the inhibitors of α-glucosidase.…”

Imaging Docking and Fusion of Insulin Granules Induced by Antidiabetes Agents

“…Sulfonylurea drugs such as glibenclamide have long been used clinically to increase insulin release in type 2 diabetes (10,11). More recently, nonsulfonylurea drugs, including glinides such as nateglinide (A-4166) and mitiglinide (KAD-1229), have become available for clinical use (12)(13)(14). It is generally accepted that both sulfonylureas and glinides induce K ATP channel closure, resulting in downstream increased intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) and subsequent insulin release.…”