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最新先天Cohen糖尿病大鼠：
表达性别差异的饮食所致的II型糖尿病的非肥胖的正常血脂的遗传模型
The newly inbred Cohen diabetic rat is an exceptional experimental
model of diet-induced type 2 diabetes mellitus that is the result
of secondary inbreeding nearly 30 years after it originally had been
established. Animals from the original colony were selectively inbred
by stringent criteria for 10 additional generations, bringing overall
inbreeding to >50 generations. The metabolic phenotypes of the
resulting contrasting strains, designated as the Cohen diabetic-sensitive
(CDs) and -resistant (CDr) rats, were characterized. The phenotype
of the CDs strain that was fed a regular diet consisted of fasting
normoglycemia, normal glucose tolerance to intraperitoneal glucose
loading, normal fasting insulin levels, and a normal insulin response
to glucose loading. In contrast, CDs rats that were fed a custom-prepared
high-sucrose low-copper diabetogenic diet became overtly diabetic:
fasting glucose levels were normal or elevated, and the blood glucose
insulin response to glucose loading was markedly abnormal. CDr rats
that were fed a regular or diabetogenic diet did not develop diabetes
and maintained normal glucose tolerance and insulin secretion. A striking
sex difference was observed in CDs rats that were fed a diabetogenic
diet: males had a lower growth rate and a more severe glucose intolerance
pattern than females. Gonadectomy shortly after weaning did not prevent
the development of the diabetic phenotype in its early phase in either
sex but markedly attenuated its expression in males at a later phase,
abolishing the sex differences. Alternate-day feeding, as opposed
to daily feeding, also attenuated the metabolic phenotype in males.
The development of the diabetic phenotype in CDs rats that were fed
a diabetogenic diet was not accompanied by obesity or hyperlipidemia.
The genetic profile of the strains was established using 550 microsatellite
markers evenly distributed throughout the rat genome. The rate of
homozygosity within strain was >/=96%. The rate of polymorphism
between the contrasting strains was 43%. We conclude that the metabolic
phenotypes of the rebred colony of CDs and CDr rats and their genetic
makeup render the Cohen diabetic rat a useful experimental model that
is highly suitable for studying the interaction between nutritional-metabolic
environmental factors and genetic susceptibility (sensitivity and
resistance) for the development of type 2 diabetes. The model is also
distinctively useful for investigating the effect of sex on the expression
of the diabetic phenotype.
【引自Diabetes 2001 Nov;50(11):2521-2529】 |
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