title: [Morphological changes of islet of Langerhans in an animal model of type 2 diabetes].
abstract: The impairment of insulin secretion, a major feature of type 2 diabetes, is caused by beta-cell mass reduction and functional failure. Pancreatic beta-cell mass reduction is variable in humans, not exceeding 50%, and has been associated with amyloid deposits. In the present study, we have chronologically compared the endocrine pancreas morphology of Wistar control rats (W) and Goto-Kakizaki (GK) rats, an animal model of non obese type 2 diabetes. We have also characterised and compared their body weight, glycaemia (fasting and after oral glucose load) as well as other biochemical parameters. GK rats were always glucose intolerant and fasting hyperglycaemia arised at four week of age. Wistar rats had mild glucose intolerance in their first two weeks of life. GK rats had a total beta-cell mass always decreased when compared to controls, but above 40%. In adult GK rats (12 weeks old) alterations in the architecture of a sub-population of islets occurred which displayed signs of prominent fibrosis, with cluster of beta-cells widely separated by strands of connective tissue and deposits of PAS positive material. Our findings demonstrate that, using GK rats from the Coimbra colony, beta-cell mass reduction is one of the primary features in the pathological sequence leading to diabetes. Structural lesions of the islets, that will further increase beta-cell mass reduction and compromise beta-cell function, will appear latter mainly due to hyperglycaemia.
authors.affiliation: Instituto de Fisiologia, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Seiça
authors.forename: M João
authors.initials: MJ
authors.lastname: Martins
authors.forename: Pedro B
authors.initials: PB
authors.lastname: Pessa
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Santos
authors.forename: Luís M do
authors.initials: LM
authors.lastname: Rosário
authors.forename: K I
authors.initials: KI
authors.lastname: Suzuki
authors.forename: Maria I
authors.initials: MI
authors.lastname: Martins
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar