Management Of Insulin Resistance Research Articles

Interleukin-6–174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients

Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position −174 ( G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6–174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 –174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients ( p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C− (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C− carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6–174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance “IL-6-sensitive”, while C− carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.

Kv1.3 potassium channel blockade as an approach to insulin resistance

Diabetes mellitus is a devastating metabolic disease caused by either insulin deficiency or resistance and characterised by abnormal glucose, protein and lipid metabolism. It affects > 150 million people worldwide, 14 million in the US alone (90% Type II and 10% Type I) where it accounts for ∼ 15% of healthcare expenditure. Insulin resistance is a cardinal feature of Type II diabetes. The molecular mechanisms that mediate insulin resistance are under intense scrutiny, and a major goal of this effort is to uncover potential therapeutic targets. Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism. Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane. In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.

Insulin Resistance and Postmenopausal Hormone Replacement Therapy

Insulin resistance causes hyperglycemia by disturbing glucose uptake in the tissues and increasing hepatic glucose production. Hyperinsulinemia has a predictive role in the generation of type 2 diabetes in nondiabetic individuals. Both insulin resistance and the associated disturbances are responsible for increased cardiovascular risk. Women of reproductive age are protected from cardiovascular disease although in the postmenopausal period the risk becomes equal to that in men and exceeds that in men later on. This observation leads us to consider the role of estrogen deficiency in the pathogenesis of cardiovascular disease. Hormone replacement therapy (HRT) is a successful method in the management of certain clinical situations in postmenopausal women. The interactions among estrogen, menopause, and cardiovascular risk bring forth the question of whether the HRT affects insulin resistance or not. The studies so far have yielded controversial results. The overall results of recent reports indicate that postmenopausal HRT improves insulin resistance. However, the available evidence is not strong enough to suggest the use of postmenopausal HRT as a first-line therapeutic measure in the management of insulin resistance.

Phytanic acid, a natural peroxisome proliferator-activated receptor (PPAR) agonist, regulates glucose metabolism in rat primary hepatocytes.

Phytanic acid, a metabolite of the chlorophyll molecule, is part of the human diet and is present in normal human serum at low micromolar concentrations. It was previously shown to be a ligand of the 9-cis-retinoic acid receptor and peroxisome proliferator-activated receptor (PPAR) a. PPAR agonists are widely used in the treatment of type 2 diabetes. Here, we report that phytanic acid is not only a transactivator of PPARa, but it also acts via PPARb and PPARg in CV-1 cells that have been cotransfected with the respective full-length receptor and an acyl-CoA oxidase-PPAR-responsive element-luciferase construct. We observed that, in contrast to other fatty acids, phytanic acid at physiological concentrations enhances uptake of 2-deoxy-D-glucose in rat primary hepatocytes. This result could be explained by the increase in mRNA expression of glucose transporters-1 and -2 and glucokinase, as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Compared with the PPARg-specific agonist ciglitazone, phytanic acid exerts only minor effects on the differentiation of C3H10T1/2 cells into mature adipocytes. These results clearly demonstrate that phytanic acid acts via different PPAR isoforms to modulate expression of genes involved in glucose metabolism, thus suggesting a potential role of phytanic acid in the management of insulin resistance.

Diagnosis and Management of Insulin Resistance in Dogs and Cats With Diabetes Mellitus

Both dogs and cats with diabetes occasionally develop resistance to the action of insulin during treatment. Clinical insulin resistance should be suspected in any animal in which marked hyperglycemia persists throughout the day despite insulin doses of greater than 1.5 U/kg per injection. In a clinical setting it may be difficult to determine the underlying cause for insulin resistance, which makes management difficult. This article reviews the known causes for insulin resistance and outlines recommendations for diagnosis and management of diabetic dogs and cats.

Management of insulin allergy and resistance

The pathophysiologic basis and therapy of insulin insensitivity and insulin allergy are discussed. Topics covered include primary and secondary causes of insulin insensitivity, management of insulin resistance (elimination of diabetogenic factors; use of less antigenic insulin, oral hypoglycemic agents, immunosuppression, or nonmammalian insulin), and insulin allergy and its treatment. A pharmacist's knowledge of insulin products and the pharmacologic activity of the oral hypoglycemic and immunosuppressive agents may aid in the care of patients who are allergic or resistant to insulin.