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 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  ).
• 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

Effects of hyperglycemia

Further Reading

Publications

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.