Role Of Impaired Insulin Action In The Pathogenesis Of Type 2 Diabetes Mellitus

In type 2 diabetes mellitus, plasma glucose levels are elevated as a result of an impairment of several metabolic pathways (29-31) (Table 1). Skeletal muscle is the principal organ for postprandial glucose uptake (29,30). In the pathogenesis of diabetes mellitus type 2, reduced insulin-stimulated glucose disposal (insulin resistance) plays a key role (21,29). When clearance of plasma glucose is impaired, blood glucose after a meal will remain slightly elevated

Table 1 Metabolic Alterations in Type 2 Diabetes

Diminished insulin-mediated peripheral glucose disposal and metabolism (insulin resistance)

Impaired insulin secretion (reduced first-phase response, prolonged second phase) Decreased insulin-mediated inhibition of lipolysis Increased gluconeogenesis and will thus induce hyperinsulinemia to overcome resistance (Fig. 1). Hyper-insulinemia, however, will evoke an alteration of the insulin-signaling cascade, which will further augment insulin resistance, thus leading to a vicious cycle (29,30).

There is an ongoing scientific discussion as to whether insulin resistance of skeletal muscle or an impairment of insulin secretion is the first and principal disorder. However, epidemiological data indicate that reduced insulin sensitivity can already be demonstrated when insulin secretion is still adequate

Genes

Physical inactivity Obesity

Genes

Physical inactivity Obesity

insulin signaling chain

Figure 1 Vicious cycle of insulin resistance and hyperinsulinemia. Due to the reduced insulin sensitivity, peripheral glucose uptake is diminished. Therefore, plasma glucose clearance is reduced, and postprandial blood glucose will remain slightly higher. This will consequently induce hyperinsulinemia to overcome the insulin resistance. Hyperinsulinemia, however, will evoke a negative modulation of the insulin signaling chain, which will further exacerbate the insulin resistance, hence leading to a vicious cycle. SNS, sympathetic nervous system.

insulin signaling chain

Figure 1 Vicious cycle of insulin resistance and hyperinsulinemia. Due to the reduced insulin sensitivity, peripheral glucose uptake is diminished. Therefore, plasma glucose clearance is reduced, and postprandial blood glucose will remain slightly higher. This will consequently induce hyperinsulinemia to overcome the insulin resistance. Hyperinsulinemia, however, will evoke a negative modulation of the insulin signaling chain, which will further exacerbate the insulin resistance, hence leading to a vicious cycle. SNS, sympathetic nervous system.

4- EDNO-formation radica! oxygen species

4- EDNO-formation

^vasodilation

^peripheral blood flow c r erations to metabolic insulin resistance contribution of A hemodynamic radical oxygen species

Glucose Î

Insulin resistance

•4- Glucose-uptake

Glucose Î

Negative modulation of the insulin signaling chain -«—

Hyperinsulinemia

Figure 2 Model of the potential pathomechanism induced by oxidative stress. Interplay between hemodynamic and metabolic alterations. EDNO, endothelium-derived nitric oxide.

(29). Thus, it is currently believed that as long as hyperinsulinemia can compensate for insulin resistance, glucose tolerance will be normal; with progressive impairment of ß-cell function, impaired glucose tolerance (iGT) or frank type 2 diabetes will be the consequence (29) (Fig. 2).

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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