Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting.

The insulin receptor (IR) and type 1 insulin-like growth factor (IGF-I) receptor (IGFR) are both widely expressed in mammalian tissues, and are known to be capable of heteromeric assembly as insulin/IGF hybrid receptors, in addition to the classically described receptors. By selective immunoadsorption of radioligand/receptor complexes and by immunoblotting we have determined the fraction of insulin receptors and IGF receptors occurring as hybrids in different tissues. Microsomal membranes were isolated from tissue homogenates and solubilized with Triton X-100. Solubilized receptors were incubated with 125I-IGF-I, and radioligand/receptor complexes bound by IR-specific and IGFR-specific monoclonal antibodies were quantified. The fraction of IGF-I binding sites behaving as hybrids (anti-IR-bound/anti-IGFR-bound) was approx. 40% in liver and spleen, 70% in placenta, and 85-90% in skeletal muscle and heart, similar results being obtained in rabbit and human tissues. There was no correlation between the proportion of hybrids and the ratio of 125I-insulin/125I-IGF-I binding in different tissues. The fraction of 125I-insulin bound to hybrids was too low for accurate quantification, because of the relatively low affinity of hybrids for insulin. The fraction of insulin receptors present in hybrids was therefore determined by immunoblotting. Receptors in solubilized human placental microsomal membranes were precipitated with IR-specific or IGFR-specific monoclonal antibodies, and after SDS/PAGE, blots were prepared and probed with IR-specific and IGFR-specific antisera. It was found that 15% of IR and 80% of IGFR were present in hybrids. Consistent with these figures, the overall level of IR was estimated, by blotting with the respective antibodies at concentrations shown to give equal signals with equal amounts of receptor, to be 4-fold greater than IGFR. Overall it was concluded that a significant fraction of both IR and IGFR occurs as hybrids in most mammalian tissues, including those that are recognized targets of insulin and IGF action. The fraction of hybrids in different tissues was not a simple function of the relative levels of IR and IGFR, possibly because of heterogeneity of receptor expression in different cell types. However, in placenta the proportions of IR, IGFR and hybrids were consistent with a process of random assembly reflecting the molar ratio of IR and IGFR half-receptors.

Hospital-physician relations: overcoming barriers to cooperation.

In the September-October 1986 issue of Physician Executive, we discussed the application of strategic business units (SBUs) to health care. SBUs are those corporate entities that market similar products to one or more target populations with similar characteristics. Examples of SBUs in health care are obstetrics, cardiology, orthopedics, etc. When the services within each SBU are linked together, they might resemble a vertically integrated health care system. In the case of obstetrics, a woman may have contact with physicians, a hospital, home care nurses, house-cleaning services, birthing teachers, and maternity clothing boutiques. Each of these are products/services within the SBU of obstetrics. Strategy development by SBU implies an external focus on the marketplace in terms of the specific mission of the SBU (clinical specialty). It also implies responding to the needs of consumers for whom the historical and present divisiveness between hospitals and physicians is immaterial and irrelevant. In this article, we will focus on ways to stabilize the relationship between hospitals and physicians within an SBU context in order to compete more successfully as a team in today's health care environment.

What business are you in?

Ths structure of the health care delivery system continues to evolve, old organizational types taking new forms and new entities joining in a sometimes helter-skelter array. What is missing is order and purpose. Most health care organizations have not yet asked the critical questions, "What business are we in?" and "Who are our customers?" The authors suggest that what is needed is a strategic business unit approach to the process of business development.