Physiology
Endocrine
Regarding insulin receptors, which of the following statements is CORRECT:
Answer:
Insulin receptors are present on most cells and they can be sequestered into the cell to inactivate them; they consist of two extracellular alpha subunits which contain the insulin-binding site and two transmembrane beta subunits. Insulin must act via cell surface receptors as it is a polypeptide hormone which cannot readily cross the cell membrane. When insulin binds to the receptor, the beta subunit autophosphorylates and activates tyrosine kinase causing an intracellular cascade of phosphorylation that results in the translocation of the glucose transporter GLUT-4 and to a lesser extent GLUT-1 to the plasma membrane of the affected cell, to facilitate the entry of glucose.Insulin Physiology
Physiology / Endocrine / Pancreatic Function
Last Updated: 2nd May 2019
Insulin is produced by Ξ² cells, located centrally within the islets of Langerhans, in the endocrine tissues of the pancreas.
Insulin is a polypeptide hormone consisting of two short chains (A and B) linked by disulphide bonds. Proinsulin is synthesised as a single-chain peptide. Within storage granules, a connecting peptide (C peptide) is removed by proteases to yield insulin. The C peptide is packaged and secreted along with insulin, and its concentration is used to monitor Ξ² cell activity in diabetic patients who receive exogenous insulin.
Insulin release is stimulated initially during eating by the parasympathetic nervous system and gut hormones such as secretin, but most output is driven by the rise in plasma glucose concentration that occurs after a meal. Circulating fatty acids, ketone bodies and amino acids augment the effect of glucose.
The major action of insulin is to stimulate glucose uptake, with the subsequent manufacture of glycogen and triglycerides by adipose, muscle and liver cells. TheΒ effects of insulin are mediated by the receptor tyrosine kinase. The enzyme activates an intracellular pathway that results in the translocation of the glucose transporter GLUT-4 and to a lesser extent GLUT-1 to the plasma membrane of the affected cell, to facilitate the entry of glucose. Insulin thus decreases plasma glucose.
Insulin release is reduced as the blood glucose concentration falls, and is further inhibited by catecholamines acting at Ξ²Β cell alpha-2-adrenoceptors.
![Insulin signal transduction pathway By James Foreman, used with permission. [CC0], from Wikimedia Commons](https://mrcemsuccess.com/wp-content/uploads/2018/08/1024px-BIOE_Article_Pic.svg_.png)
Insulin Signal Transduction Pathway. (Image by James Foreman, used with permission. [CC0], from Wikimedia Commons)
Comparison between Insulin and Glucagon
| Hormone | Insulin | Glucagon |
|---|---|---|
| Cell Type | Beta-cells | Alpha-cells |
| Factors that Increase Secretion |
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| Factors that Decrease Secretion |
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| Mechanism of Action | Acts on tyrosine kinase receptor to activate intracellular pathway that results in translocation of GLUT-4 transporter to plasma membrane | Acts on G-protein coupled receptor to stimulate production of cAMP |
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Major Actions |
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| Overall Effect on Blood Levels |
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 ΞΌmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 ΞΌmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
