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Pharmacology

Endocrine

Question 26 of 180

Which of the following is NOT an action of insulin:

Answer:

Insulin acts to:
  • Increase cellular glucose uptake
  • Decrease gluconeogenesis
  • Increase glycogenesis/decrease glycogenolysis
  • Increase lipogenesis/decrease lipolysis
  • Increase protein synthesis/decrease proteolysis
  • Increase cellular potassium uptake

Insulin Physiology

Insulin is produced by β 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 β 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. The 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 β cell alpha-2-adrenoceptors.

Insulin signal transduction pathway By James Foreman, used with permission. [CC0], from Wikimedia Commons

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
  • ↑ Blood glucose
  • ↑ Amino acids
  • ↑ Fatty acids
  • Glucagon
  • Secretin
  • Acetylcholine
  • ↓ Blood glucose
  • ↑ Amino acids
  • Cholecystokinin
  • Catecholamines
  • Acetylcholine
Factors that Decrease Secretion
  • ↓ Blood glucose
  • Somatostatin
  • Catecholamines
  • ↑ Blood glucose
  • Insulin
  • Somatostatin
  • Fatty acids, ketoacids
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

Major Actions

  • ↑ Glucose uptake into cells
  • ↑ Glycogenesis
  • Glycogenolysis
  • ↓ Gluconeogenesis
  • ↑ Protein synthesis
  • ↓ Protein degradation
  • ↑ Fat deposition
  • ↓ Lipolysis
  • ↓ Ketoacid production
  • ↑ K+ uptake into cells
  • ↓ Glycogenesis
  • ↑ Glycogenolysis
  • ↑ Gluconeogenesis
  • ↓ Fatty acid synthesis
  • ↑ Lipolysis
  • ↑ Ketoacid production
Overall Effect on Blood Levels
  • ↓ [Glucose]
  • ↓ [Amino acid]
  • ↓ [Fatty acid]
  • ↓ [Ketoacid]
  • ↓ [K+]
  • ↑ [Glucose]
  • ↑ [Fatty acid]
  • ↑ [Ketoacid]

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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 μmol/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 μmol/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

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