Is defective pancreatic beta-cell mass environmentally programmed in Goto-Kakizaki rat model of type 2 diabetes?: insights from crossbreeding studies during suckling period.
OBJECTIVE
The Goto-Kakizaki (GK) rat is a spontaneous model of type 2 diabetes with a well established pathological pancreatic beta-cell development. Hyperglycemia experienced during early postnatal life contributes to the programming of endocrine pancreas. We have analyzed the consequences of hyperglycemic versus euglycemic suckling period for the pancreatic beta-cell mass and the in vivo glucose tolerance and insulin secretion in 4-week-old unweaned control Wistar (W), diabetic GK, and in offspring issued from crosses between normoglycemic W and diabetic GK rats.


METHODS
Mother/father crosses yielded offspring designated as follows: W/W, GK/GK, W/GK, and GK/W. In vivo glucose tolerance and insulin secretion tests were performed on males 4 weeks after birth, that is, just before weaning. Beta-cell mass was determined by immunohistochemistry and morphometry.


RESULTS
Four-week-old W/GK and GK/W rats are normoglycemic, normoinsulinemic, and display a similarly small beta-cell mass. Both W/GK and GK/W rats exhibit in vivo glucose intolerance and defective insulin secretion in response to glucose.


CONCLUSIONS
Our data obtained from crossbreeding studies during suckling period suggest that the defective pancreatic beta-cell mass is not environmentally programmed in the GK model of type 2 diabetes. Rather, they support the hypothesis that the beta-cell mass defect in the GK is linked to genetic determinism.
Calderari
Sophie
S
Laboratoire de Physiopathologie de la Nutrition, UMR CNRS 7059, Université Paris 7, Paris, France.
Gangnerau
Marie-Noëlle
MN
Meile
Marie-José
MJ
Portha
Bernard
B
Serradas
Patricia
P
D000818:Animals; D000833:Animals, Suckling; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood / Q000235:genetics / Q000473:pathology; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006824:Hybridization, Genetic; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D007774:Lactation / Q000378:metabolism; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose