Lack of insulin receptors affects the formation of white adipose tissue in mice. A morphometric and ultrastructural analysis.
Lack of insulin receptors in mice is associated with near-normal intrauterine growth, unlike patients with leprechaunism, in whom growth deficiency is a prominent clinical feature. Genetic crosses of insulin receptor- and insulin-like growth-factor-1 (IGF-1) receptor-deficient mice indicate, however, that insulin receptors play an important role in late gestational growth, and that absence of growth retardation in insulin receptor-deficient (IR-/-) mice may be due to a compensatory increase in IGF-1 receptor levels. In human fetuses, insulin has a paramount role in the generation and maintenance of adipose tissue, as demonstrated by changes associated with genetic and maternally caused fetal hyperinsulinaemia. In the present study, we have investigated whether genetic ablation of insulin receptors affects differentiation and trophism of white adipose tissue, the main target organ for the growth-promoting actions of fetal insulin. Histological, immunohistochemical, and ultrastructural analyses of white dermal adipose tissue were performed in newborn IR-/- mice, as well as normal (IR +/+ ) and heterozygous controls (IR+/-). Stereological measurements revealed a marked decrease of the adipose area in IR-/- mice compared to IR+/+ and IR+/- mice. Fat cell depletion resulted mainly from a reduction of adipocyte volume ( approximately 90 %), with a small decrease of adipocyte number. Electron microscopy analysis detected all stages of differentiation of the adipocyte precursor in IR-/- mice, suggesting that lack of insulin receptors is not associated with selective impairment of the adipocyte differentiation process. These data are consistent with a bi-modal action of fetal insulin receptors, one to mediate embryonic growth in response to IGF-2, and one to mediate adipose cell formation in response to insulin.
Cinti
S
S
Istituto di Morfologia Umana Normale, Facoltá di Medicina e Chirurgia, Universitá di Ancona, Italy.
Eberbach
S
S
Castellucci
M
M
Accili
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D
D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D011972:Receptor, Insulin / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000378:metabolism / Q000648:ultrastructure
D011972:Receptor, Insulin