D. Rabinowitz

Isolated human growth hormone deficiency. III. Insulin secretion in sexual ateliotic dwarfism

Abstract Among 24 subjects with monotropic HGH deficiency, two groups can be defined on the basis of sensitivity to exogenous insulin and of the plasma insulin response to provocative stimuli. The majority (Group I) exhibit insulin sensitivity, and insulinopenia after intravenous arginine administration and after ingestion of glucose. Short term growth hormone treatment augments the insulin response to glucose, an effect which is not accountable for by the degree of peripheral hyperglycemia. Results from Group I sexual ateliotics are in agreement with the previously suggested insulinotropic effect of HGH, and suggest that in addition to its anti-insulin action, HGH may have a direct insulinotropic effect upon the pancreatic beta cell. Four sexual ateliotics (Group II) show greater than normal insulin responses to glucose and to arginine, and do not exhibit sensitivity to exogenous insulin. The circulation of an altered growth hormone molecule, possessing selective biological activity but being undetectable by immunological assay, could account for these findings.

Effect of arginine on insulin release in vitro

Abstract The effect of arginine on insulin release was studied by observing the effect of glucose and arginine, both singly and together, on the release of immuno insulin from pieces of rabbit pancreas incubated in bicarbonate buffer. Arginine alone (1.0–3.0 mg./ml.) failed to stimulate insulin release above control levels, whereas the same pancreas when subsequently exposed to a glucose concentration of 3.0 or 3.5 mg./ml. showed a convincing response. When ariginine was tested in buffer fortified with 1.5 mg./ml. glucose, it significantly enhanced insulin release. These data suggest that arginine influences insulin release by enhancing the stimulatory effect of the glucose metabolite(s) which triggers insulin release in the B-cell.

FLUX OF PALMITIC ACID ACROSS THE ADIPOSE TISSUE MEMBRANE

I t was the purpose of this investigation to determine whether or not the flux of palmitic acid into and out of adipose tissue from rat epididymal fat pads could be described by a model of purely passive processes. To do this, one needs to measure not only the fluxes but also the driving forces: chemical, electrical and possibly other fonts of potential energy. It is not difficult to measure the fluxes, nor is it impossible to measure the driving forces for influx, but owing to uncertainties about the internal chemical organization of the adipose cell, it is so far impossible to assess the driving forces for efflux. For this reason, although we will report our measurement of efflux, we cannot determine whether or not is is purely passive, as we can do for the case of influx. We will also present data on some of the factors that modify flux of palmitic acid, particularly the roles of glucose and insulin insofar as we have been able to define them in a preliminary way. The principle underlying our measurement of fluxes is illustrated in FIGURE 1. Region 1 is free palmitic acid outside the adipose cell. Free palmitic acid is also inside the adipose cell, but its distribution may be heterogeneous so that an unknown portion of it is sequestered. Some of the intracellular free palmitic acid constitutes region 2, defined by the fact that these are the molecules that will be translocated to the outside and that will be enriched by flux from the outside. Influx of palmitic acid is p12, in units of mass per time, and efflux is p z l . Region 3 contains palmitic acid incarcerated in glycerides, and, as we shall see, serves as a sink. Region 4 is another fraction of free palmitic acid. Its molecules may be formed by synthesis from substrates in region 5 and may be dissimilated into products such as COs that form region 6. Presumably region 4 is also linked with glycerides in region 3 and may also be linked with the other free palmitic acid region. Since there may be information that demands further complication of the model, on the right hand portion of the FIGURE there are supplied spare parts, squares and arrows.

Isolated human growth hormone deficiency. IV. The response of sexual ateliotic dwarfs to exogenous growth hormone

Abstract Sexual ateliotic dwarfs react acutely to human growth hormone treatment with a decrease in nitrogen and phosphorus excretion, a fall in serum urea nitrogen, and a rise in urinary calcium. The plasma insulin response to glucose is considerably augmented. A single subject, treated for one year, has exhibited an impressive increase in linear growth.