Pharmacological Approach in the Treatment of Insulin Resistance

Abstract

Insulin resistance syndromes are heterogeneous in either severity or mechanism. Many drugs have been shown to counteract various elements of insulin resistance. Some of them, by normalization of metabolic parameters, decrease insulin resistance induced by chronic hyperglycemia in diabetes. Insulin and, to some extent, sulfonylureas are in this group, but these drugs are not stricto sensu medication of insulin resistance. Some drugs sensitize peripheral tissues to the action of insulin. For instance, biguanides and thiazolidine-dione facilitate translocation to the membrane of glucose transporter in presence of insulin. Other compounds as vanadate or IGF-1 mimic some peripheral action of insulin. Finally, blockade of FFA oxidation by specific inhibitors (methylpalmoxyrate) can limit insulin resistance. In 1992, among these compounds, specific of insulin resistance, biguanides are mostly used. However, the efficacy of these drugs is moderate and limited to type 2 diabetes.

Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention*1

“…[1][2][3][4] Insulin sensitizers act by decreasing endogenous and exogenous insulin requirements and have other potentially beneficial effects on the cardiovascular system. [5][6][7][8][9][10][11][12][13][14][15][16] We hypothesized that diabetic patients enrolled in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) Trial and treated with metformin would demonstrate a lower adverse event rate than diabetic patients treated with non-insulin-sensitizing medications.…”

Pharmacological means of influencing insulin resistance (a review)

“…The interest of researchers in this subject is explained by the fact that the spreading of diabetes mellitus (DM) has acquired an epidemic character.According to the pathophysiological mechanism of appearance of non-insulin-dependent diabetes mellitus (NIDDM), this form of DM can arise both from a reduced level of insulin secretion by the pancreatic 13-cells and from increased levels of glucose production in the liver and stability of peripheral tissues with respect to insulin [1][2][3][4][5]25]. The latter factor, known as insulin resistance, is accompanied by violated glucose tolerance and leads to the development of obesity and arterial hypertension.…”

“…Therefore, the glucose concentration in the blood plasma can be normalized by increasing the insulin level. This can be achieved both by introducing exogenous hormone and by stimulating insulin secretion by the pancreatic [3-cells using drugs of the sulfonylurea group [2]. However, should the chronic hyperglycemia be induced by the insulin resistance, we arrive at a "closed circle" situation where hyperglycemia and hyperinsulinemia would coexist.…”

“…However, should the chronic hyperglycemia be induced by the insulin resistance, we arrive at a "closed circle" situation where hyperglycemia and hyperinsulinemia would coexist. For this reason, insulin and sulfonylurea derivatives are not the principal means of correcting the resistance of tissues to this hormone [2,9,25,28].…”

“…The second group contains substances of pepfide nature, which are capable of producing insulinlike action. These are the insulinlike growth factor 1 (IGF-1) and the human growth hormone fragment hGH [2,9,31], as well as some organic and inorganic compounds of vanadium [2,9,28]. The third group represents the inhibitors of anti-insulin agents (glueagon) such as amylin analogs [9] and some others.…”