The HND mouse, a nonobese model of type 2 diabetes mellitus with impaired insulin secretion.
OBJECTIVE
This study aimed to develop a novel type 2 diabetes model designated the HND (Horio-Niki diabetic) mouse, by transferring diabetogenic genes from wild castaneus mice (Mus musculus castaneus) captured in the Philippines into laboratory mice (C57BL/6J:B6).


METHODS
Offspring from the cross between a wild male and a B6 female were backcrossed to the sire. One male backcross which exhibited fasting hyperglycemia was crossed with a B6 female to comprise the fundamental stock (F0). Thereafter, full-sib mating was performed, and mice with impaired glucose tolerance were selected and bred from the F2 generation. Characterization of the phenotype of HND mice and insulin release from their islets was evaluated with F12 generation males.


RESULTS
The male HND mice were lean, and spontaneously exhibited impaired glucose tolerance at a high incidence rate at 6 weeks of age. Their serum insulin levels in response to intraperitoneal glucose were markedly attenuated. However, glucose-induced insulin release from isolated HND islets was not affected. Notably, inhibition of glucose-induced insulin release by epinephrine was more pronounced in HND islets than in B6 islets. Moreover, in vivo treatment of HND mice with the alpha2-adrenergic receptor agonist clonidine resulted in marked hypoinsulinemic hyperglycemia.


CONCLUSIONS
We suggest the HND mouse may be a distinctive and useful model for type 2 diabetes with impaired neural control of insulin secretion.
Horio
Fumihiko
F
Department of Food and Nutritional Sciences, College of Bioscience and Biotechnology, Chubu University, Matsumoto-cho 1200, Kasugai 487-8501, Japan. horiof@isc.chubu.ac.jp
Teradaira
Shin
S
Imamura
Tsunehiko
T
Anunciado
Rea Victoria P
RV
Kobayashi
Misato
M
Namikawa
Takao
T
Niki
Ichiro
I
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000835:Animals, Wild; D001786:Blood Glucose / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004837:Epinephrine; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D001786:Blood Glucose; D007328:Insulin; D015016:Yohimbine; D003000:Clonidine; D004837:Epinephrine