Type 2 diabetes - a matter of failing beta-cell neogenesis? Clues from the GK rat model.
Now that reduction in beta-cell mass has been clearly established in humans with type 2 diabetes mellitus (T2D), the debate focuses on the possible mechanisms responsible for decreased beta-cell number. Appropriate inbred rodent models are essential tools for this purpose. The information available from the Goto-Kakizaki (GK) rat, one of the best characterized animal models of spontaneous T2D, is reviewed in such a perspective. We propose that the defective beta-cell mass in the GK model reflects mostly a persistently decreased beta-cell neogenesis. The data discussed in this review are consistent with the notion that poor proliferation and/or survival of the endocrine precursor cells during GK foetal life will result in a decreased pool of endocrine precursors in the pancreas, and hence an impaired capacity of beta-cell neogenesis (either primary in the foetus or compensatory in the newborn and the adult). As we also demonstrated that beta-cell neogenesis can be pharmacologically reactivated in the GK model, our work supports, on a more prospective basis, the concept that facilitation of T2D treatment may be obtained through beta-cell mass expansion after stimulation of beta-cell regeneration/neogenesis in diabetic patients.
Movassat
J
J
Laboratoire de Physiopathologie de la Nutrition, Université Paris Diderot/Paris 7, Paris, France.
Calderari
S
S
Fernández
E
E
Martín
M A
MA
Escrivá
F
F
Plachot
C
C
Gangnerau
M N
MN
Serradas
P
P
Alvarez
C
C
Portha
B
B
D000818:Animals; D001786:Blood Glucose; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D010179:Pancreas / Q000196:embryology*; D010180:Pancreatectomy; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin