ISSN 2398-2942      

Diabetes mellitus: pathophysiology


Audrey K Cook

Normal glucose regulation


  • The pancreas has important exocrine and endocrine functions.
  • The endocrine tissue is located within the Islets of Langerhans.
  • Within the Islets, four distinct cell types, each with a different endocrine function, are recognized:
    • Alpha cells produce glucagon.
    • Beta cells produce insulin.
    • Delta cells produce somatostatin.
    • F or PP cells produce pancreatic polypeptide.
  • The cells are organized in a very structured way within the Islets with a central core of beta cells surrounded by a ring of the other endocrine cells.

Insulin production

  • The initial product of the beta cells is proinsulin (an inactive form).
  • Insulin is cleaved from proinsulin with the liberation of C peptide.
  • Insulin and C peptide pass into the portal circulation; 50% of the insulin is immediately removed by the liver.
  • In the normal fasting animal, insulin concentrations in the blood are <20 U/l.
  • Insulin secretion is stimulated by a number of factors:
    • Increased glucose concentrations.
    • Gastrointestinal hormones, eg secretin, gastrin, cholecystokinin and the incretins (glucose-dependent insulinotrophic polypeptide and glucagon-like peptide-1).
    • Beta-adrenergic stimulation.
  • Catecholamines and somatostatin reduce insulin secretion.
  • The secretions from all the cells in the Islets are closely interregulated.

Insulin interaction with receptors

  • Insulin binds to specific cell membrane receptors in target tissues (muscle and adipose) resulting in autophosphorylation of the receptor which activates intracellular proteins facilitating glucose entry into cells.
  • Once activated, the receptor - insulin complex is internalized in the cell and insulin is degraded.
  • Entry of glucose into brain cells occurs by diffusion without the influence of insulin.
  • Cell receptor numbers may change.
  • Chronic exposure to insulin results in down-regulation of receptors, but when insulin is scarce the receptor numbers increase.

Action of insulin

  • Insulin produces anabolic effects (see diagram Endocrinology plasma glucose regulation - diagram ).
  • In liver tissue, insulin stimulates synthesis of glycogen, protein and triglycerides and inhibits catabolism.
  • In muscle tissue, insulin increases amino acid transport and protein synthesis.
  • In adipose tissue, it increases triacylglycerol storage.

Diabetes mellitus

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Effects of hyperglycemia

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Further Reading


Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Catchpole B, Kennedy L J, Davison L J et al (2008) Canine diabetes mellitus: from phenotype to genotype. JSAP 49 (1), 4-10 PubMed.
  • Fall T, Johansson Kreuger S, Juberget A et al (2008) Gestational diabetes mellitus in 13 dogs. JVIM 22 (6), 1296-1300 PubMed.
  • Guptill L, Glickman L & Glickman N (2003) Time trends and risk factors for diabetes mellitus in dogs: analysis of vet medical data base records (1970-1999). Vet J 165 (3), 240-247 PubMed.

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