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Biomedical subjects

J Bornstein

Publications and source records attributed to J Bornstein.

At least 91 records · Page 5Linked to original sources
PubMed1982

Comparison of hypoglycaemic responses to human growth hormone and the synthetic 4-15 fragment between 16-18 day-old and 45-50 day-old rats.

The hypoglycaemic response to human growth hormone and its synthetic 4-15 fragment were studied in 16-18 day-old and 45-50 day-old normal male rats using three different bioassay system: (1) intravenous insulin tolerance tests, (2) insulin binding to specific receptor of hepatic plasma membranes, and (3) activation of insulin-dependent glycogen synthase in muscle. The mean level of the endogenous growth hormone in the 16-18 day-old group was 11 +/- 4 ng/ml and that of the 45-50 day-old group was 164 +/- 35 ng/ml. A hypoglycaemic action of human growth hormone was observed in the baby animals but not in the adults. The synthetic 4-15 fragment was found, at a similar dose to that of the intact molecule, to enhance hypoglycaemia in both groups of rats. In exact parallel, growth hormone increased hepatic insulin binding and activated muscle glycogen synthase only in baby rats but the synthetic 4-15 fragment affected both baby and adult animals in the same way. The molecular mechanism for the diminution of the responses to the intact molecule of growth hormone in normal adult rats remains to be identified. However, the present studies provide the first evidence on the hypoglycaemic response to growth hormone in vivo in normal rats without any previous chemical or surgical treatment.

Aging↗
PubMed1982

Effect of C-terminal chain shortening on the insulin-antagonistic activity of human growth hormone 177--191.

Six synthetic C-terminal shortened fragments of the reduced and S-carbamidomethylated peptide corresponding to residues 177 to 191 of human growth hormone (Cam-hGH 177--191) were assayed for insulin antagonistic activity in vivo. Two of the peptides, Cam-hGH 177--191 and cam-hGH 177--191 were, in nanomolar quantities, both active in that they caused significant hyperglycaemia and insulin resistance in normal rats. The remaining peptides, hGH 177--180, Cam-hGH 177--185, Cam-hGH 177--187 and hGH 177--189 were all inactive even at up to one hundred times the dose employed for the active peptides. The results indicate that an insulin antagonistic core of hGH is contained within amino acid residues 178 to 190 inclusive.

Amino Acid Sequence↗
PubMed1981

Human urinary insulin-potentiating peptide: immunological evidence for the absence of the human growth hormone amino terminal sequence, Phe-Pro-Thr-Ile-Pro-.

The immunological reactivities of synthetic partial sequences of human growth hormone (hGH) and of an insulin-potentiating peptide isolated from human urine were studied using an antiserum raised against a synthetic hGH analogue [beta-Ala13]hGH(1-15). This antiserum contained antibodies directed mainly against a determinant in the sequence hGH(1-5). It was found that synthetic peptides containing the sequence Phe-Pro-Thr-Ile-Pro- (residues 1-5 of hGH) were immunologically active. Of the biologically active peptides studied, the synthetic peptide hGH(6-13) was virtually inactive and the urinary peptide was completely inert. Absence of immunologically detectable cross-reactivity lends support to the hypothesis that the amino acid sequence of urinary insulin-potentiating peptide (U-AcG) does not contain the hGH amino terminal sequence, Phe-Pro-Thr-Ile-Pro-.

Amino Acid Sequence↗
PubMed1981

Insulin-potentiating action of human growth hormone. Synthesis and activity of N-terminal fragments.

Four peptides from the N-terminal region of human growth hormone have been synthesized by the solid-phase method: hGH(6-13), hGH(7-13), hGH(8-13) and hGH(9-13). Although these peptides contain the sensitive -Asp-Asn-sequence, apparently homogeneous products were obtained by synthesis on polystyrene resin, cleavage by hydrogen fluoride and purification by ion-exchange chromatography. The insulin-potentiating activity of these peptides is reported. The data indicates that extension of hGH(9-13) at its N-terminus is required for in vitro activity.

Amino Acid Sequence↗
PubMed1981

Intravenous solutions in parenteral nutrition.

A review of the theoretical basis on which amino acid intravenous solutions are formulated leads to the conclusion that the first class protein model is not ideal for the very small premature infant. Comparison of the serum and urine amino acid levels in a controlled trial between intravenous feeding with "Vamin" and intragastric milk feeding, and further comparison of these values with the cord blood values of premature infants supports the conclusion that the first class protein model is not ideal. The balance studies also support the view that the urinary output of amino acids, as well as the serum levels, should be taken into account in determining the ideal amino acid input.

Amino Acids↗
PubMed1980

The minimal amino acid sequence of the insulin-potentiating fragments of human growth hormone: its mechanism of action.

A series of synthetic peptides corresponding to the amino-terminal sequence of human growth hormone (hGH) has been studied for insulin-potentiating effects using three different bioassay systems: (1) intravenous insulin tolerance tests, (2) insulin binding to specific receptors of hepatic plasma membranes and isolated hepatocytes, and (3) modulation of insulin-dependent glycogen synthase and glycogen phosphorylase in muscle and adipose tissue. The results establish that the minimum active sequence is the hexapeptide (hGH 8-13) containing H2N-Arg-Leu-Phe-Asp-Asn-Ala-COOH and strongly indicate that the insulin-potentiating action of the active peptides is to increase the binding of insulin to specific receptors and thus modulate the action of glycogen synthase and phosphorylase, producing hypoglycemia as the result of increased glycogen storage in liver, muscle, and adipose tissue.

Adipose Tissue↗
PubMed1979

Diabetogenic action of human growth hormone. Synthesis and activity of C-terminal fragments.

Three peptides corresponding to the C-terminal region of human growth hormone have been synthesized by the solid-phase method: HGH-(177--191), HGH-(178--191) and HGH-(179--191). The diabetogenic activities of these synthetic peptides are reported. The data indicate that extension of HGH-(179--191) at its NH2-terminus is required for in vivo activity. The reduced and S-carbamidomethylated form of HGH-(177--191) was also active, indicating that the disulphide bond is possibly not a prerequisite for biological activity.

Amino Acid Sequence↗
PubMed1979

HLA patterns in Australian patients with insulin dependent diabetes mellitus (IDDM).

HLA antigens were determined in 169 Australian patients with insulin dependent diabetes mellitus (IDDM). HLA-B8 (47.9% v. 23.8%) and B15 (18.9% v. 8.2%) were significantly more frequent in the IDDM patients than in 1460 controls. The relative risks for developing IDDM in people carrying these antigens were 2.94 and 2.59 respectively. Carriers of the B8/B15 genotype had a relative risk of 5.48. These HLA associations in Australian IDDM patients are similar to those reported in other predominantly Caucasian populations.

Adolescent↗
PubMed1979

Effect of synthetic C-terminal fragments of hGH on glucose oxidation by isolated islets.

The effect of polypeptides containing the human growth hormone sequence 177--191 on the glucose metabolism of isolated islets of Langerhans has been investigated. It has been found that such peptides accelerate the incorporation of hydrogen at carbon atom 5 into water while accelerating the flux (1-14C oxidation) through the pentose phosphate shunt and inhibiting the oxidation of [6-14C]glucose. The latter inhibition was found not to be due to inhibition of the pyruvate dehydrogenase complex, and it was further found that the previously demonstrated potentiation of glucose-induced insulin release by the peptides was independent of energy provision because none of the glyceraldehyde, pyruvate, or leucine could substitute for glucose. In view of the fact that the insulinogogue effect of this peptide is to potentiate the glucose stimulatory effect on islets, these phenomena may well be unrelated.

Animals↗
PubMed1979

Insulin-potentiating action of a synthetic amino-terminal fragment of human growth hormone (hGH 1--15) in streptozotocin-diabetic rats.

The hypoglycemic activity of the synthetic peptide fragment of human growth hormone, hGH 1--15, is insulin dependent, although it does not alter the circulating levels of plasma insulin in normal and diabetic rats. In severe diabetes induced by streptozotocin, the peptide had no effect on the basal levels of blood glucose, but enhanced insulin sensitivity during intravenous insulin tolerance tests in 16-h-fasted rats. Radioreceptor binding studies show increased binding of insulin by hepatic plasma membranes prepared from rats pretreated with hGH 1--15. These results suggest that the biologic action of the peptide is, at least in part, on insulin receptors of plasma membranes.

Animals↗
PubMed1978

Effects of part sequences of human growth hormone on in vivo hepatic glycogen metabolism in the rat.

Acute effects of two part sequences of human growth hormone on the in vivo activity levels of hepatic glycogen synthase and glycogen phosphorylase were examined. The peptide corresponding to residues 6 to 13 of the hormone (hGH 6--13) decreased the percentage of phosphorylase in the active form without affecting synthase activity. This action was indirect and dependent upon insulin. The peptide hGH 177--191 decreased the level of the active form of synthase without affecting phosphorylase activity. This effect was also observed with analogous peptides containing the sequence hGH 178--191 (i.e., hGH 172--191 and hGH 178--191), whereas the peptide hGH 179--191 was inert. The onset of these effects was rapid, and maximum changes in activity were produced in 5 min by both peptides. The effect for hGH 177--191 was short-lived, and synthase activity had returned to normal levels by 15 min, whereas the action of hGH 6--13 was of longer duration and was still quite marked at 60 min. Both peptides showed a linear dependence of response to the log dose of peptide injected over the range 0.1--250 microgram hGH 6--13 per kg body weight and 0.05--25 microgram hGH 177--191 per kg body weight. Hepatic 3',5'-cyclicadenylic acid levels were not affected by either peptide. Incorporation of glycerol carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH 177--191. This is discussed in terms of a futile cycle between glycogen and hexose phosphate in the liver, as the basis for a control mechanism for hepatic glycogen metabolism. The present observations are consistent with other in vivo and in vitro actions of these and related peptides.

Amino Acid Sequence↗
PubMed1978

Hyperglycemic action of synthetic C-terminal fragments of human growth hormone.

The synthetic peptides corresponding to amino acids 172-191, 176-191, 177-191, 178-191, 179-191, and 180-191 of human growth hormone (hGH) have been studied for their in vivo effects in normal rats. Four of the peptides (hGH 172-191, 176-191, 177-191, and 178-191) produced a short-lived rise in blood glucose and a more sustained rise in plasma insulin, whereas the other two (hGH 179-191 and 180-191) were inert in the systems tested. A single dose (5 nmol/kg body wt) of the peptides containing the amino acids sequence 178-191 of the hGH molecule significantly reduced insulin sensitivity of the animals in intravenous insulin tolerance tests. The findings also indicate that the biologically active peptides must not only have the minimum of the informational sequence but also that this must be in correct physical configuration.

Blood Glucose↗
PubMed1978

Effect of synthetic C-terminal fragments of hGH on insulin release by isolated islets.

Synthetic fragments representing the C-terminal end of the growth hormone molecule have been tested for their direct in vitro effects on insulin release by isolated rat islets of Langerhans. hGH 177-191 caused a dose-related potentiation of glucose-induced insulin release, whereas the peptide by itself caused no stimulation of insulin release from the islets. The rate curves constructed for insulin secretion as a function of extracellular glucose concentration showed that the Km for glucose is not altered in the presence of the peptide, but that the Vmax of secretion is increased. Significant potentiation of insulin release by the peptide was seen only at high extracellular concentrations of glucose. Measurement of cAMP levels in islets showed that the peptide caused no significant alteration of cAMP levels while still potentiating insulin release. It was therefore concluded that the mechanism of potentiation of insulin release by the peptide may be independent of the changes in cAMP levels in islets. hGH 172-191, too, caused potentiation of glucose-stimulated insulin release from islets, whereas hGH 179-191 was not active in this report.

Animals↗