Felis ISSN 2398-2950

Diabetes mellitus: pathophysiology

Contributor(s): David Bruyette, Audrey K Cook

Normal glucose regulation

Introduction

  • 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 pro-insulin (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 glucogon-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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Classification of diabetes mellitus

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Niessen S J (2010) Feline acromegaly: an essential differential diagnosis for the difficult diabetic. J Fel Med Surg 12 (1), 15-23 PubMed.
  • Slingerland L I, Fazilova V V, Plantinga E A et al (2009) Indoor confinement and physical inactivity rather than the proportion of dry food are risk factors in the development of feline type 2 diabetes mellitus. Vet J 179 (2), 247-253 PubMed.
  • McCann T M, Simpson K E, Shaw D J et al (2007) Feline diabetes melllitus in the UK; the prevalence within an insured cat population and a questionnaire-based putative risk factor analysis. J Fel Med Surg (4), 289-299 PubMed.
  • Rand J S, Fleeman L M, Farrow H A et al (2004) Canine and feline diabetes mellitus: nature or nuture? J Nutr 134 (8 Suppl), 2072S-2080S PubMed.
  • Zoran D L (2002) The carnivore connection to nutrition in cats. JAVMA 221 (11), 1559-1567 PubMed.


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