TISSUE-SPECIFIC ALTERATIONS IN G-PROTEIN EXPRESSION IN GENETIC VERSUSDIET-INDUCED MODELS OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS IN THEMOUSE

Various tissues were obtained from the well-characterized genetic mode l (C57BL/6J-ob/ob) of non-insulin-dependent diabetes mellitus (NIDDM) and from a diet-induced model of NIDDM produced in the same genetic ba ckground (C57BL/6J). The objectives were to determine whether the prev iously observed changes in guanine nucleotide-binding regulatory prote in (G protein) expression in adipose tissue from ob/ob mice were mirro red by concomitant changes in other tissues, and whether NIDDM of a di fferent etiology would share similar alterations in G protein expressi on. Plasma membranes from adipocytes, brain, heart, liver, and testes were probed with alpha-subunit-specific antisera, and the level of G p rotein expression in each model was compared with that in its lean lit termate control. Adipose, heart, and liver cell membranes from ob/ob m ice contained significantly less alpha-subunit of stimulatory G protei n (G(s) alpha) than those from their lean littermates. As compared wit h the lean littermates, heart alpha-subunit-2 of inhibitory G protein (G(i) alpha-2), liver G(i) alpha-3, and adipocyte G(1) alpha-1 and G(i ) alpha-3 were also reduced in ob/ob mice. In contrast, G(i) alpha-2 a nd G(o) alpha were increased over lean-control levels in brain tissue from ob/ob mice, whereas G(s) alpha was unchanged. G protein expressio n in the testes did not differ between lean and ob/ob mice. In the die t-induced model of NIDDM, G(s) alpha expression in the liver was twofo ld greater in obese/diabetic mice as compared with lean controls. Howe ver, G protein expression in all other tissues examined did not differ between obese/diabetic animals and lean littermates. Although the sev erity of overt symptoms of NIDDM is comparable between the two models, the diet-induced model does not suffer from the documented endocrine abnormalities of hypothyroidism and hyperadrenocorticism noted in the ob/ob mouse. Thus, it seems likely that the G protein changes noted in the ob/ob mouse are not the direct result of the obese or diabetic co ndition, but may be secondary to endocrine differences between the two models. Copyright (C) 1995 by W.B. Saunders Company