Insulin-sensitizing agents

Sleep A class of drug that were developed as insulin-sensitizing agents and are currently used for the treatment of type 2 diabetes. They have been shown to bind to and activate the y isoform of the PPARs, which is particularly expressed in adipocytes, and appear to function in part by stimulating the release of... 

A conventional treatment algorithm involving clomiphene citrate (CC) followed by FSH induction of ovulation may result in a 71% cumulative single-ton live birth rate. In attempts to improve treatment outcome further and reduce complication rates, new compounds such as insulin-sensitizing agents or aro-matase inhibitors (Letrozole) are currently used increasingly. 

Two subclasses of insulin-sensitizing agents are currently available, the biguanidesand the thiazolidinediones. They are described separately in this section because drugs in these... 

Yoshimoto T, Naruse M, Shizume H, et al. Vasculo-protective effects of insulin sensitizing agent pioglitazone in neointimal thickening and hypertensive vascular hypertrophy. Atherosclerosis. 1999 145 333-340. 

Injectable recombinant human insulin-like growth factor (rhIGF-I rINN mecasermin) has been available for nearly 20 years for treatment of the rare instances of growth hormone (GH) insensitivity caused by GH receptor defects or GH-inhibiting antibodies. It has also been used as an insulin-sensitizing agent in severe insulin-resistant conditions. Adverse reactions to mecasermin have been reviewed [24 ]. The most common adverse reaction is hypoglycemia, which is readily controlled by administration with meals. 

These agents activate PPAR-y a nuclear transcription factor important in fat cell differentiation and fatty acid metabolism. PPAR-yagonists enhance insulin sensitivity in muscle, liver, and fat tissues indirectly. Insulin must be present in significant quantities for these actions to occur. 

Fluid retention may occur, perhaps as a result of peripheral vasodilation and/or improved insulin sensitization with a resultant increase in renal sodium and water retention. A dilutional anemia may result, which does not require treatment. Edema is reported in 4% to 5% of patients when glitazones are used alone or with other oral agents. When used in combination with insulin, the incidence of edema is about 15%. Glitazones are contraindicated in patients with New York Heart Association Class III and IV heart failure and should be used with great caution in patients with Class I or II heart failure or other underlying cardiac disease. 

Somatostatin stimulant Insulin sensitizer Anti-inflammatory agents... 

I have already mentioned leptin. There are several others, notably including adiponectin, a protein present in high concentrations in blood. Adiponectin is an antihyperglycemic agent, acting to increase insulin sensitivity. There is a close relationship between obesity, insulin action, and development of type 2 diabetes. Withont listing additional peptides secreted by adipose tissue, it is important to understand that fat is an important player in human physiology. 

Thiazolidinediones are the newer agents that favourably influence insulin sensitivity and possibly also pancreatic fS-cell function. The biological response of thiazolidinediones is mediated by binding to the nuclear peroxisome proliferator-activated receptor-y (PPAR)... 

Complications of diabetes FBG, HbAjC/ insulin sensitivity Some oral antidiabetic agents... 

Pharmacology Rosiglitazone and pioglitazone, members of the thiazolidinediones class of antidiabetic agents, improve glycemic control by improving insulin sensitivity. Studies indicate that they improve sensitivity to insulin in muscle and adipose tissue and inhibit hepatic gluconeogenesis. 

Rosiglitazone, a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. 

Recently, resveratrol was found to reverse fat-induced insulin resistance [McCarty, 2005]. This observation provides more enthusiasm for researchers to use resveratrol as an antidiabetic agent. Su and associates [2006] showed that resveratrol significantly reduced the plasma glucose concentration as well as the dramatic reduction of triglyceride concentration in streptozotocin (STZ)-induced diabetic mellitus rats in 14 days treatment. They concluded from this observation that resveratrol possesses hypoglycemic and hypolipidemic properties [Su et al., 2006]. Baur et al., [2006] added more value to this conclusion by showing that resveratrol increases insulin sensitivity by lowering the blood... 

Metformin, another agent with insulin-sensitizing effects, was found in retrospective analysis to have decreased rates of death and Ml (OR = 0.29 P = 0.007 and OR = 0.3 I... 

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