David Rabinowitz

Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man.

To investigate the role of glucagon in regulating hepatic glucose production in man, selective glucagon deficiency was produced in four normal men by infusing somatostatin (0.9 mg/h) and regular pork insulin (150-muU/kg per min) for 2 h. Exogenous glucose was infused to maintain euglycemia. Arterial plasma glucagon levels fell by greater than 50% whereas plasma insulin levels were maintained in the range of 10-14 muU/ml. In response to these hormonal changes, net splanchnic glucose production (NSGP) fell by 75% and remained suppressed for the duration of the study. In contrast, when somatostatin alone was administered to normal men, resulting in combined insulin and glucagon deficiency (euglycemia again maintained), NSGP fell markedly but only transiently, reaching its nadir at 15 min. Thereafter, NSGP rose progressively, reaching the basal rate at 105 min. These data indicate that the induction of selective glucagon deficiency in man (with basal insulin levels maintained) is associated with a marked and sustained fall in hepatic glucose production. We conclude, therefore, that basal glucagon plays an important role in the maintenance of basal hepatic glucose production in normal man.

The carcinoid flush. Provocation by pentagastrin and inhibition by somatostatin.

THE carcinoid syndrome is characterized by episodes of flushing that appear to be secondary to the secretion of one or more substances by a tumor of enterochromaffin-cell origin.1 2 3 Flushing can ...

Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate.

Dichloroacetate is known to reduce plasma cholesterol and triglyceride in patients with Fredrickson Types IIb or IV hyperlipoproteinemia. We now report the effects of chronic, oral dichloroacetate administration (as the sodium salt) in two patients with severe homozygous familial hypercholesterolemia. Dichloroacetate markedly reduced serum total and low density lipoprotein cholesterol levels and lowered the low density lipoprotein to high density lipoprotein cholesterol ratio. One patient developed a polyneuropathy while receiving dichloroacetate which resolved following discontinuation of the drug. Because of its apparent toxicity, dichloroacetate cannot be recommended for chronic oral use. Investigation of the mechanism of its lipid-lowering effect, however, may provide insight into the pathogenesis and treatment of hypercholesterolemic disorders.

Peripheral Subresponsiveness to Human Growth Hormone in the African Pygmies

Abstract The African pygmies, an ethnic group characterized by proportionate shortness of stature, attain normal plasma concentrations of human growth hormone (HGH) after arginine infusion and insu...

Isolated follicle-stimulating hormone deficiency revisited. Ovulation and conception in presence of circulating antibody to follicle-stimulating hormone.

WE have previously described the clinical features of a 22-year-old woman who was evaluated in 1971 for primary amenorrhea and in whom we established the diagnosis of isolated deficiency of follicl...

Chromatin-positive Klinefelter's syndrome with undetectable peripheral FSH levels

An 18 year old phenotypic man is described with chromatin-positive Klinefelters syndrome and undetectable peripheral human follicle stimulating hormone levels. The subject manifested chromosomal mosaicism consisting of three stem cell lines (45X; 46XY; and 47XXY). Testicular biopsy specimen showed germinal cell aplasia: the tubules were lined by Sertoli cells only, whereas the Leydig cells appeared normal. Serum human follicle stimulating hormone levels were undetectable and rose to only 5 mIU/ml after the administration of luteinizing hormone releasing hormone. Serum human luteinizing hormone varied between normal and moderately elevated values, and serum testosterone was in the low normal range. We discuss the features which distinguish this syndrome from isolated gonadotropin deficiency and from classic germinal cell aplasia. We suggest that the patient represents a new variant of Klinefelters syndrome, with failure of human follicle stimulating hormone release secondary to prolonged hypersecretion.

Concanavalin-A stimulates human chorionic gonadotrop in (hCG) and hCG-alpha secretion by human choriocarcinoma cells☆

Abstract The plant lectin Concanavalin-A stimulates the secretion of human chorionic gonadotropin and free alpha subunit by cultured human choriocarcinoma cells in a dose dependent and time dependent manner. This stimulation is prevented by alpha-methyl-D-mannopyranoside, a Concanavalin-A specific hapten sugar. This is the first report of a lectin stimulating the secretion of a glycoprotein hormone. Since the stimulation likely occurs subsequent to interactions at the membrane level, Concanavalin-A may represent a probe for studying membrane-related events involved in the control of human chorionic gonadotropin secretion.

Blue Dextran: Influence on Chromatographic Profile and Immunoreactivity of Human Follicle-Stimulating Hormone (HFSH)

Summary When FSH is chromatographed on G-100 Sephadex in the absence of Blue Dextran, it elutes as a single peak in the region of monomeric FSH. The addition of Blue Dextran causes a significant portion of FSH, iodinated or uniodinated, to elute in the region of the void volume. When standard curves for FSH are performed under identical conditions, with tracer 125I-FSH from the void volume, and from the FSH monomer region, maximal immunoreactivity was significantly greater for the Blue Dextran-associated tracer. This work was supported by Chief Scientist, Israeli Ministry of Health, Mifal Hapayis, and Population Council.