Treatment insulin sensitizers

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... 

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. 

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. 

Metformin works best in patients with significant hyperglycemia and is often considered first-line therapy in the treatment of mild to moderate type II overweight diabetics who demonstrate insulin resistance. The United Kingdom Prospective Diabetes Study demonstrated a marked reduction in cardiovascular comorbidities and diabetic complications in metformin-treated individuals. Metformin has also been used to treat hirsutism in individuals with polycystic ovarian syndrome and may enhance fertility in these women, perhaps by decreasing androgen levels and enhancing insulin sensitivity. 

Figueras, M., Olivan, M., Busquets, S., Lopez-Soriano, F., and Argiles, J. (2011). Effects of eicosapentaenoic acid (EPA) treatment on insulin sensitivity in an animal model of diabetes Improvement of the inflammatory status. Obesity 19, 362-369. 

In some instances, transdermal estrogens appear less likely to cause problems than other forms of administration. One group studied the treatment of polycystic ovary syndrome in 24 women, using transdermal or peroral administration of a combination of estradiol and cypro-terone acetate in doses comparable to those used in oral contraceptives (217). The peroral treatment led to a significant impairment in insulin secretion and action whereas the transdermal application of estrogens did not significantly influence insulin sensitivity. 

Viytovich MH, Simonsen C, Jenssen T, Hjelmesaeth J, Asberg A, Hartsmann A. Short-term treatment with rosiglitazone improves glucose tolerance, 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... 

Treatment with either vanadium salts or organic complexes of vanadium have decreased plasma insulin levels and improved insulin sensitivity in animal models of both insulin resistance and type 2 diabetes. This work has recently been reviewed [13]. The Zucker Diabetic Fatty (ZDF) rat develops overt hyperglycemia in the presence of hyperinsulinemia followed by [3-cell depletion. This is a type 2 diabetic rat model developed from the Zucker Fatty (fa/fa) rat. In these animals, chronic treatment with vanadium reduced the elevated plasma glucose levels [152,153], The effect in the type 2 models of diabetes can take weeks to develop, whereas the effect in the type 1 models of diabetes are seen within 3 to 4 days. 

We have observed that suppression of elevated FFA levels is a very rapid (less than 12 hour) response to treatment of insulin-resistant rats with PPARy agonists (T. Doebber, unpublished data). Since PPARy agonists are known to promote adipose tissue uptake and storage of fatty acids, it is plausible that this effect constitutes a major mechanism of insulin sensitization, whereby elevated FFAs—a known cause of hepatic and muscle insulin resistance—can be alleviated. An additional effect of in vivo PPARy activation, shown to occur in rats, was an increase in the number of small white adipocytes, along with a relative shift in the size of visceral (decreased) versus subcutaneous (increased) adipose depots (73). This has important implications because visceral adiposity and larger fat cells are both associated with insulin resistance. 

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