Insulin

Clinic

• Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the INS gene.
• It is the main anabolic hormone. Circulating insulin affects protein synthesis in tissues Low insulin levels have opposite effect by promoting widespread catabolism, esp on reserve body fat.
• It also regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells.
• Glycogenesis / Lipogenesis: Conversion of absorbed Glucose / Triglycerides into glycogen in the liver.
• Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.
• Beta cells are sensitive to blood sugar levels so that they secrete insulin into the blood in response to high level of glucose, and inhibit secretion of insulin when glucose levels are low.
• Insulin enhances glucose uptake and metabolism in the cells, thereby reducing blood sugar level.
• Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.
• Glucagon increases blood glucose level by stimulating glycogenolysis and gluconeogenesis in the liver. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis.

Diabetes mellitus

• Decreased or absent insulin activity results in Diabetes mellitus / Hyperglycaemia.
• There are two types of the disease. In T1DM, the beta cells are destroyed by an autoimmune reaction so that insulin can no longer be synthesized or be secreted into the blood.
• In T2DM, there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. Also peripheral tissue insulin resistance is known to be involved. Increased glucagon secretion which is unaffected by, and unresponsive to the concentration of blood glucose is also seen. But insulin is still secreted into the blood in response to the blood glucose. As a result, glucose accumulates in the blood.

Oscillations

Insulin release from pancreas oscillates with a period of 3–6 minutes.

Physiological effects

The actions of insulin on the global human metabolism level include:

• Increase of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about two-thirds of body cells)
• Increase of DNA replication and protein synthesis via control of amino acid uptake
• Modification of the activity of numerous enzymes.

The actions of insulin (indirect and direct) on cells include:

• Stimulates the uptake of glucose
• Increased fat synthesis
• Increased esterification of fatty acids – forces adipose tissue to make neutral fats (i.e., triglycerides) from fatty acids; decrease of insulin causes the reverse.
• Decreased lipolysis
• Induced glycogen synthesis
• Decreased gluconeogenesis and glycogenolysis / Decreases production of glucose from noncarbohydrate substrates, primarily in the liver
• Decreased proteolysis
• Decreased autophagy
• Increased amino acid uptake – forces cells to absorb circulating amino acids; decrease of insulin inhibits absorption.
• Decreased arterial muscle tone/ Increasing blood flow, esp microarteries
• Increase in the secretion of hydrochloric acid by parietal cells in the stomach
• Increased potassium uptake
• Decreased renal sodium excretion.

• Insulin also influences other body functions, such as vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular. Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the co-ordination of a wide variety of homeostatic or regulatory processes in the human body.
• Insulin also has stimulatory effects on GnRH from the hypothalamus

Diseases and syndromes

• Diabetes mellitus
  • T1DM
  • T2DM
• Insulinoma – a tumor of beta cells producing excess insulin or reactive hypoglycemia.
• Metabolic syndrome: Elevated blood pressure + Dyslipidemia + Increased waist circumference+ Insulin resistance. It is common for morbidities such as essential hypertension, obesity, type 2 diabetes, and cardiovascular disease (CVD) to develop.
• PCOS: Insulin resistance is present.
• Insulin resistance syndrome