What Is Insulin?

Insulin is a peptide hormone of 51 amino acids essential for the uptake of glucose into the hepatic, adipose and muscle tissues. It is responsible for maintaining normal glucose metabolism, but also plays a role in fat metabolism.

Insulin is released from the pancreatic β-cells present in the islets of Langerhans in response to elevated blood glucose levels. Glucose initially binds to the GLUT-2 transporters present on the pancreatic β-cell membranes, initiating a cascade of cellular changes to release insulin from densely packed vesicles.

Insulin binds as a ligand to tyrosine kinase receptors, initiating a cascade of biochemical events so that insulin can perform its various metabolic functions. These receptors have an extracellular domain for insulin to bind to and an intracellular domain that initiates the relative cellular changes.

When insulin is deficient or ineffective, such as with diabetes and insulin resistance, its absence causes the suppression of glucose transporters. This results in the ineffective uptake of glucose, leaving post prandial blood glucose levels elevated for longer. Insulin resistance is the term used when body cells no longer respond well to the insulin hormone.

When insulin no longer functions well, the body compensates with the additional release of insulin from the pancreatic β-cells to maintain normal blood glucose levels. If this compensatory release of insulin is no longer effective in overcoming the body cells’ weak response, average blood glucose levels can rise and lead to the development of prediabetes and type 2 diabetes. Diabetes Canada noted that insulin resistance is an integral component in the pathophysiology of type 2 diabetes. Insulin resistance with hyperinsulinemia and deteriorating glycaemic control may assist in the accumulation of triglycerides and thus further reduced insulin sensitivity.

Insulin resistance is considered a polygenic, multifactorial disorder. It is a consequence of genetic and / or various lifestyle factors such as overweight or obesity, physical inactivity, being 45 years and older, having a parent or sibling with diabetes and having a history of other health related conditions such as cardiovascular disease, stroke, elevated cholesterol, high blood pressure, polycystic ovary syndrome (PCOS), sleep apnoea, Cushing’s syndrome, acanthosis nigricans and acromegaly. Certain medication such as glucorticoids, antipsychotics and anti-retroviral agents also seem to increase risk for insulin insensitivity.

Excessive fat mass is a major factor considered to increase the risk for developing insulin resistance. This particularly refers to a high visceral fat content, reflected in a large waist circumference, even when body mass index (BMI) is within normal range. Visceral adipose tissue has been found to release various compounds that can result in chronic low-grade inflammation – which is associated with insulin resistance, type 2 diabetes and cardiovascular disease.

• Moderate weight loss is important if overweight or obesity is present – this is described as losing about 5-7 percent of the current body weight. The International Diabetes Federation (IDF) recommends a 5-10 percent weight loss in the first year of treatment.
• Increased physical activity is noted as an important component in the improvement of insulin sensitivity. It can assist with weight reduction and weight maintenance whilst possibly improving other metabolic markers coinciding with insulin resistance, diabetes and metabolic syndrome. Resistance training, especially when supervised by a professional, has been found to reduce insulin sensitivity although the combination of aerobic and resistance training is said to have an additive effect on glycaemic control.
• The IDF thirdly recommends a change in dietary composition.

Dietary patterns such as the Nordic Diet has been found to improve insulin resistance in three “high quality randomized controlled trials”. The Nordic Diet is considered a Nordic translation of the Mediterranean, Portfolio, DASH and NCEP dietary principles. “It emphasizes ≥25% energy as whole-grain products, ≥175 g/day temperate fruits (apples and pears), ≥150 to 200 g/day berries (lingonberries and blueberry jam), ≥175 g/day vegetables, legumes (beans, peas, chickpeas and lentils), canola oil, ≥3 servings/week fatty fish (salmon, herring and mackerel), ≥2 servings/day low-fat dairy products, as well as several of the LDL-C-lowering foods common to the Portfolio Diet, including nuts (almonds), viscous fibres (oats, barley, psyllium), and vegetable protein (soy)”.

As highlighted by the IDF, these include drug therapy to target insulin resistance, impaired glucose tolerance and prediabetes. The Diabetes Prevention Program (DPP) has shown that metformin therapy can assist in preventing the onset of type 2 diabetes while recent thiazolidinedione studies have shown promise to do the same via its interaction with PPARG receptors.

Other emerging therapies include incretin mimetics, dipeptidyl peptidase IV inhibitors, protein tyrosine phosphatase 1B inhibitors, and the endocannabinoid receptor blocking agents for combating obesity.