Everything About Insulin and Insulin Resistance

  • As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. The study of insulin and insulin resistance remain in the forefront of medical research.
  • Rapid globalization, urbanization and industrialization have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and “convenience” foods unmask latent predisposing genetic traits.
  • Understanding the role of insulin across a wide range of physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in populations today.
  • We may need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialization and sleep patterns.

Main Definitions and Concepts

  • Insulin is a peptide hormone secreted by the β cells of the pancreatic islets of Langerhans and maintains normal blood glucose levels by facilitating cellular glucose uptake, regulating carbohydrate, lipid and protein metabolism and promoting cell division and growth through its mitogenic effects.
  • Insulin resistance is defined where a normal or elevated insulin level produces an diminished biological response; classically this refers to impaired sensitivity to insulin mediated glucose disposal.
  • Compensatory hyperinsulinemia (High Insulin levels in blood) occurs when pancreatic β cell secretion increases to maintain normal blood glucose levels in the setting of peripheral insulin resistance in muscle and adipose tissue.
  • Insulin resistance is when cells in your muscles, body fat and liver start resisting or ignoring the signal that the hormone insulin is trying to send out—which is to grab glucose out of the bloodstream and put it into our cells. 
  • As insulin resistance develops, your body fights back by producing more insulin. Over months and years, the beta cells in your pancreas that are working so hard to make insulin get worn out and can no longer keep pace with the demand for more and more insulin. Then – years after insulin resistance silently began – your blood sugar may begin to rise and you may develop prediabetes or type 2 diabetes. You may also develop non-alcoholic fatty liver disease (NAFLD), a growing problem associated with insulin resistance that boosts your risk for liver damage and heart disease. 

Synthesis and Release of Insulin

  • Given insulin’s pivotal role in glucose utilization and metabolism, it is not surprising that glucose has multiple influences on insulin biosynthesis and secretion.
  • Glucose is the principal stimulus for insulin secretion, though other macronutrients, hormones, humoral factors and neural input may modify this response.
  • Insulin, together with its principal counter-regulatory hormone glucagon, regulates blood glucose concentrations.
  • The first phase of insulin secretion represents release of insulin already synthesized and stored in secretory granules; the second phase represents secretion of both stored and newly synthesized insulin.
  • Insulin mediates its actions through binding to insulin receptors located in various tissues and organs in the body. Insulin transports various nutrients and delivers to various tissue cells through insulin receptors.
  • Insulin acts at multiple steps in carbohydrate metabolism. Its effect on facilitated diffusion of glucose into fat and muscle cells.
  • Insulin stimulates fatty acid synthesis in adipose tissue, liver and lactating mammary glands along with formation and storage of triglycerides in adipose tissue and liver.
  • Insulin promotes protein synthesis in a range of tissues.
  • Insulin is the pivotal hormone regulating cellular energy supply and macronutrient balance, directing anabolic processes of the fed state. Insulin is essential for the intra-cellular transport of glucose into insulin-dependent tissues such as muscle and adipose tissue.
  • Signaling abundance of exogenous energy, adipose tissue fat breakdown is suppressed. Insulin therefore promotes glycogen and lipid synthesis in muscle cells, while suppressing lipolysis (Fat burning) and gluconeogenesis (generation of glucose from certain non-carbohydrate carbon substrates)  from muscle amino acids. Hence, In the presence of an adequate supply of amino acids, insulin is anabolic in muscle.

Causes of Insulin Resistance

Things that can make this condition more likely include:

  • Obesity, especially belly fat or visceral fat
  • Inactive lifestyle or sedentary lifestyle
  • Imbalanced Diet
  • Deficiency in key Micro-Nutrients (Vitamins/Minerals)
  • Irregular eating habits
  • Smoking
  • Drinking excess alcohol
  • Hormonal disorders like Cushing’s syndrome and acromegaly
  • Medications like steroids, antipsychotics, and HIV medications
  • Insufficient rest and sleep
  • Chronic Stress and Anxiety
  • Pregnancy

Health Conditions Associated with Insulin Resistance

  • Type 2 Diabetes
  • Metabolic Syndrome
    • Abdominal obesity or High Visceral Fat
      • Men: waist circumference >40 inches (102 cm )
      • Women: waist circumference >35 inches (88 cm)
    • Fasting glucose ≥ 110 <126 mg/dL (6.1–7.0 mmol/L)
    • Blood pressure ≥ 130/80 mmHg
    • High Triglycerides >150 mg/dL (>1.7 mmol/L)
    • Low HDL cholesterol
      • Men <40 mg/dL (<1.0 mmol/L)
      • Women <50 mg/dL (<1.3 mmol/L)
  • PCOS – Polycystic ovary syndrome
  • Non-alcoholic Fatty Liver Disease (NAFLD)
  • Certain Cancers like including colon, endometrial, possibly pancreatic and renal-cell cancer and breast cancer.
  • Sleep disorders or Sleep Apnea.
  • Insulin acts on your brain to increase appetite and specifically an appetite for sugar.
  • It increases LDL cholesterol, lowers HDL cholesterol, raises triglycerides and increases your blood pressure. Insulin resistance causes 50% of all reported cases of high blood pressure.
  • It stimulates the growth of cancer cells.
  • It increases inflammation and oxidative stress and ages your brain.
  • It also causes sex hormone problems and can lead to infertility, hair growth where you don’t want it, hair loss where you don’t want to lose it, acne, and low testosterone in men and more. It also leads to mood disturbances.

~Praveen Jada

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