Insulin Resistance


Insulin resistance develops when the insulin in our body loses its effectiveness. It indicates a pre-diabetic state, leads to type 2 diabetes and increases the risk of heart disease.

Obesity is the main driver of insulin resistance. Increasing prevalence of obesity globally has triggered a parallel increase in insulin resistance. Genetics and environmental factors play a role in insulin resistance; it clusters with other symptoms of the metabolic syndrome.

What does insulin do?

Insulin is a hormone made by islet cells in the pancreas and secreted into the blood. Insulin mainly acts by enabling cells – such as fat cells and muscle cells – to take up free glucose and use it for energy.

Insulin suppresses the production of glucose and very low density lipoprotein – this has an an impact on fat transport in blood – in the liver. It also inhibits glucose release from the liver and the release of free fatty acids from fat stores in adipose tissue. Insulin stimulates the making of new proteins from free amino acids.

Insulin acts through the binding to a specific membrane receptor and the activation of one of two protein signalling cascades. The first regulates intermediary metabolism and the other controls growth processes and cell division. InsuIin resistance resut with interference in one of these pathways.

What is insulin resistance?

Insulin resistance occurs when the body fails to respond to insulin as effectively as it should. The body needs much higher than normal levels of insulin; so the pancreas compensates by trying to produce more insulin.

Degrees of insulin resistance exist with considerable variation in inter-individual insulin sensitivity. Mild insulin resistance is within the realms of normality, and moderate insulin resistance only damages some individuals in the presence of other risk factors. However, insulin resistance is insidious when progressive or severe.

Resistance occurs in response to the body’s own insulin (endogenous) or when insulin is administered by injection (exogenous). If the insulin the body produces is less effective, then the body cells do not produce enough energy. The pancreas continues producing even more insulin to compensate, which is equally ineffective.

Liver cells help keep glucose levels stable. If there is too little glucose then they make more and if there is too much insulin tells them to make less. Because the cells do not get enough glucose, the liver produces more glucose. So if there is a problem with insulin then glucose keeps getting made no matter what the level.

Environmental Causes of Insulin Resistance

Being obese is a definite risk factor for insulin resistance. Visceral adiposity is mooted as a possible central environmental factor to developing insulin resistance. Excess weight and lack of physical activity exacerbate insulin resistance when it does occur.

Genetic Causes

The role of genetics in insulin resistance is more common in certain populations. Ethnic groups more likely to have insulin resistance include Latino, African-American, Native American, and Asian-American groups.

Epidemiologic and family studies show genetic influences in insulin resistance. Mutations in PPAR gamma – involved in the insulin signalling pathway – and the insulin receptor gene  cause more extreme forms of insulin resistance. More moderate cases of insulin resistance result from the presence of polygenic and heterogeneous variants of proteins involved in insulin signalling.

Consequences of Insulin Resistance

Hyperglycaemia is the major consequence of insulin resistance. Insulin resistance is often considered to be a pre-diabetic state, Continuous hyperglycaemia can precipitate type 2 diabetes. Prolonged hyperglycaemia causes damage to tissues, hypertension, lipid disorders, the metabolic syndrome and cardiovascular disease. Some damage relates to the inflammation associated with insulin resistance.

Combating Insulin Resistance

Insulin resistance is managed with diet, exercise and proper medication. Reducing hyperglycaemia using  metformin and thiazolidinediones has had some success. The latter may also reduce inflammation associated with insulin resistance. Other medications target obesity, cardiovascular symptoms and metabolic risk factors. Endocannabinoid antagonists reduce insulin resistance and obesity.

Future new therapy targets include the steps in the insulin signalling pathways. The recent discovery of the role of PTEN gene product in insulin sensitivity may offer an insight into how insulin resistance occurs and the ability to develop new medications.

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  1. Obesity and Insulin Resistance | Dr. Robin's Corner - August 10, 2013

    […] Insulin Resistance (conorcaffrey.wordpress.com) […]

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