beta-cell function and viability in the spontaneously diabetic GK rat: information from the GK/Par colony.
The GK rat model of type 2 diabetes is especially convenient to dissect the pathogenic mechanism necessary for the emergence of overt diabetes because all adult rats obtained in our department (GK/Par colony) to date have stable basal mild hyperglycemia and because overt diabetes is preceded by a period of normoglycemia, ranging from birth to weaning. The purpose of this article is to sum up the information so far available related to the biology of the beta-cell in the GK/Par rat. In terms of beta-cell function, there is no major intrinsic secretory defect in the prediabetic GK/Par beta-cell, and the lack of beta-cell reactivity to glucose (which reflects multiple intracellular abnormalities), as seen during the adult period when the GK/Par rats are overtly diabetic, represents an acquired defect (perhaps glucotoxicity). In terms of beta-cell population, the earliest alteration so far detected in the GK/Par rat targets the size of the beta-cell population. Several convergent data suggest that the permanently reduced beta-cell mass in the GK/Par rat reflects a limitation of beta-cell neogenesis during early fetal life, and it is conceivable that some genes among the set involved in GK diabetes belong to the subset of genes controlling early beta-cell development.
Portha
B
B
Laboratoire de Physiopathologie de la Nutrition, CNRS ESA 7059, Université D. Diderot, Paris, France. portha@paris7.jussieu.fr
Giroix
M H
MH
Serradas
P
P
Gangnerau
M N
MN
Movassat
J
J
Rajas
F
F
Bailbe
D
D
Plachot
C
C
Mithieux
G
G
Marie
J C
JC
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D005952:Glucose-6-Phosphatase / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007930:Leucine / Q000494:pharmacology; D008297:Male; D008940:Mitotic Index; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D004247:DNA; D005952:Glucose-6-Phosphatase; D007930:Leucine; D005947:Glucose