1. The intraperitoneal injection of 100 μU. of insulin together with a tracer amount of glucose-U-C-14, also injected imraperitoneally, resulted over a period of two hours in a three- to fivefold increase in the incorporation of labeled glucose carbon into the glycogen of diaphragm-or epididymal adipose tissue. When the dose of insulin injected was 10,000 μU., the incorporation of glucose carbon into diaphragm was increased twenty-five- to fiftyfold, and that into epididymal fat glycogen ten- to twentyfold. These doses of insulin injected intraperitoneally were without effect upon tissues not in direct contact with the peritoneal cavity, such as heart muscle, trapezius muscle, and subscapular brown fat, while incorporation of labeled glucose into liver was either unaffected or decreased. These results were qualitatively and quantitatively similar, whether the trace amount of labeled glucose was injected intraperitoneally or intravenously.
2. When the same amounts of insulin were injected intravenously instead of intraperitoneally, together with a Jrace amount of labeled glucose, the pattern of tissue responsiveness was totally different, a small effect upon glucose carbon incorporation into glycogen being observed in only two tissues, the rhythmically contracting diaphragm and heart muscle tissues.
3. When the animals were fasted prior to the intraperitoneal injections of glucose without or with insulin, the responsiveness to insulin of diaphragm muscle was either unchanged or increased, while the response of epididymal adipose tissue to insulin decreased, this decrease being quite marked after a seventy-two-hour period of fasting.
4. These results obtained in vivo tend to support the hypothesis of the importance of insulin “binding” to tissues as a factor controlling the responsiveness of individual tissues to insulin. The results also indicate that in vivo rat diaphragm muscle is at least as sensitive to insulin as rat epididymal adipose tissue, if not more so.