Fragments Of Human Growth Hormone Research Articles

Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza.

Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16-amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6-amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy. LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection. Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship. These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage. Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage.

Establishment of a PCR-SSP method for the simultaneous amplification and identification of the presence of KIR genes

To develop a polymerase chain reaction-sequence specific primer (PCR-SSP) method for simultaneous amplification and identification of the KIR genes among Chinese population. Peripheral blood samples from 132 healthy donors who had given blood at Shenzhen Blood Center from January 2015 to November 2015 were selected as the study subjects. Based on the polymorphism and single nucleotide polymorphism (SNP) information of high-resolution KIR alleles in the Chinese population and the IPD-KIR database, specific primers were designed to amplify all the 16 KIR genes and the 2DS4-Normal and 2DS4-Deleted subtypes. The specificity of each pair of PCR primers was verified by using samples with known KIR genotypes. During PCR amplification of the KIR gene, co-amplification the fragment of human growth hormone (HGH) gene by multiplex PCR was used as the internal control to prevent false negative results. A total of 132 samples with known KIR genotypes were randomly selected for blind inspection to verify the reliability of the developed method. The designed primers can specifically amplify the corresponding KIR genes, with clear and bright bands for the internal control and KIR genes. The results of detection are fully consistent with the known results. The KIR PCR-SSP method established in this study can yield accurate results for the identification of the presence of KIR genes.

Naturally derived cytokine peptides limit virus replication and severe disease during influenza A virus infection.

Novel host-targeted therapeutics could treat severe influenza A virus (IAV) infections, with reduced risk of drug resistance. LAT8881 is a synthetic form of the naturally occurring C-terminal fragment of human growth hormone. Acting independently of the growth hormone receptor, it can reduce inflammation-induced damage and promote tissue repair in an animal model of osteoarthritis. LAT8881 has been assessed in clinical trials for the treatment of obesity and neuropathy and has an excellent safety profile. We investigated the potential for LAT8881, its metabolite LAT9991F and LAT7771 derived from prolactin, a growth hormone structural homologue, to treat severe IAV infection. LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection. In vitro LAT8881 treatment enhanced cell viability, particularly in the presence of cytotoxic stress, which was countered by siRNA inhibition of host lanthionine synthetase C-like proteins. Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages. LAT8881 treatment in combination with the antiviral oseltamivir phosphate led to more pronounced reduction in markers of disease severity than treatment with either compound alone. These studies provide the first evidence identifying LAT8881 and LAT9991F as novel host-protective therapies that improve survival, limit viral replication, reduce local inflammation and curtail tissue damage during severe IAV infection. Evaluation of LAT8881 and LAT9991F in other infectious and inflammatory conditions of the airways is warranted.

Thiol–Disulfide Exchange in Peptides Derived from Human Growth Hormone During Lyophilization and Storage in the Solid State

Lyophilization (freeze-drying) is frequently used to stabilize protein therapeutics. However, covalent modifications such as thiol-disulfide exchange and disulfide scrambling can occur even in the solid state. The effects of lyophilization and storage of lyophilized powders on the mechanism and kinetics of thiol-disulfide exchange have not been elucidated and are explored here. Reaction kinetics was monitored in peptides corresponding to tryptic fragments of human growth hormone (T20 + T20-T21 or T20 + cT20-T21) during different stages of lyophilization and during storage of the lyophilized powders at 22°C and ambient RH. The concentrations of reactants and products were determined using RP-HPLC and product identity confirmed using liquid chromatography-mass spectrometry. Loss of native disulfide was observed for the reaction of T20 with both linear (T20-T21) and cyclic (cT20-T21) peptides during the primary drying step; however, the native disulfides were regenerated during secondary drying with no further change till the end of lyophilization. Deviations from Arrhenius parameters predicted from solution studies and the absence of buffer effects during lyophilization suggest that factors such as temperature, initial peptide concentration, buffer type, and concentration do not influence thiol-disulfide exchange during lyophilization. Results from a "cold finger" method used to study peptide adsorption to ice indicate that there is no preferential adsorption to the ice surface and that its presence may not influence disulfide reactivity during primary drying. Overall, reaction rates and product distribution differ for the reaction of T20 with T20-T21 or cT20-T21 in the solid state and aqueous solution, whereas the mechanism of thiol-disulfide remains unchanged. Increased reactivity of the cyclic peptide in the solid state suggests that peptide cyclization does not offer protection against lyophilization and that damage induced by a process stress further affects storage stability at 22°C and ambient RH.

Detection and in vitro metabolism of AOD9604.

AOD9604 is a peptide consisting of the C-terminal fragment of human growth hormone from amino acids 177-191 with an additional tyrosine residue at the N-terminus of the peptide. It is reported to mimic the lipolytic properties of growth hormone without the diabetogenic side effects. Therefore, AOD9604 may be used as a performance enhancing drug and is banned by the World Anti-doping Agency (WADA). The peptide is available on several Internet websites and was recently identified in confiscated vials in the USA. To detect abuse of the peptide in athletes, a solid-phase extraction method was validated in urine with a limit of detection of 50 pg/mL. The method has good linearity, precision (<20%), specificity and recovery (62%). Six potential metabolites of the peptide were identified after incubation of AOD9604 in serum and urine. Quantification of the metabolites in serum identified a single metabolite, consisting of amino acids CRSVEGSCG, which is significantly more stable than the other metabolites or the parent compound. Screening for AOD9604 and the stable metabolite may potentially allow an increased window of detection.

Generation of 5 and 17 kDa human growth hormone fragments through limited proteolysis

Introduction. The reported presence of two fragments of 5 and 17 kDa originating from the 22 kDa human growth hormone (hGH) in blood and tissues, postulated as the sequences AA1–43 and AA44–191, has led to the hypothesis of a post-translational proteolytic origin with respect to the abundant 22 kDa variant (AA1–191). To evaluate this hypothesis, the activity of several endo-proteases on the 22 kDa hGH protein has been evaluated. Methods. Proteolysis using pepsin, trypsin, V8-protease, proteinase K and thermolysin were explored under several conditions, including incubation time and pH. Results were monitored by MALDI-TOF and HPLC-ESI mass spectrometry. Proteolytic 5 and 17 kDa fragments were purified through reversed phase HPLC-UV, and their immuno-affinity properties evaluated by surface plasmon resonance. Results. Thermolysin was shown to target mainly the AA43–44 bond of the 22 kDa sequence at physiological pH. Interaction studies of the purified fragments with anti-GH antibodies showed some reactivity for the 17 kDa fragment. Conclusions. Thermolysin processes hGH generating 5 and 17 kDa fragments, demonstrating the feasibility of this reaction, although the enzyme responsible for this process in humans is still unknown. Specific antibodies should be used to detect these fragments in human specimens, and, at the same time, the 17 kDa fragment could constitute an interference in some hGH immunoassays.

Coordinate Inhibition of Cytokine-mediated Induction of Ferritin H, Manganese Superoxide Dismutase, and Interleukin-6 by the Adenovirus E1A Oncogene

Adenovirus E1A sensitizes cells to the cytotoxic action of tumor necrosis factor alpha (TNF-alpha). This effect has been attributed to direct blockade of NF-kappaB activation, as well as to increased activation of components of the apoptotic pathway and decreases in inhibitors of apoptosis. In this report we evaluated the mechanism by which E1A modulates the expression of the cytokine-inducible cytoprotective genes manganese superoxide dismutase (MnSOD), interleukin-6 (IL-6), and ferritin heavy chain (FH). We observed that E1A blocks induction of MnSOD, IL-6, and FH by TNF-alpha or IL-1alpha. Because NF-kappaB plays a role in cytokine-dependent induction of MnSOD, IL-6, and FH, we assessed the effect of E1A on NF-kappaB in cells treated with TNF. IkappaB, the inhibitor of NF-kappaB, was degraded similarly in the presence and absence of E1A. TNF induced a quantitatively and temporally equivalent activation of NF-kappaB in control and E1A-transfected cells. However, TNF-dependent acetylation of NF-kappaB was diminished in cells expressing E1A. E1A mutants unable to bind p400 or the Rb family proteins were still capable of repressing TNF-dependent induction of FH. However, mutants of E1A that abrogated binding of p300/CBP blocked the ability of E1A to repress TNF-dependent induction of FH. These results suggest that p300/CBP is a critical control point in NF-kappaB-dependent transcriptional regulation of cytoprotective genes by cytokines.

Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism.

A small synthetic peptide sequence of human growth hormone (hGH), AOD-9401, has lipolytic and antilipogenic activity similar to that of the intact hormone. Here we report its effect on lipid metabolism in rodent models of obesity and in human adipose tissue to assess its potential as a pharmacological agent for the treatment of human obesity. C57BL/6J (ob/ob) mice were orally treated with either saline (n = 8) or AOD-9401 (n = 10) for 30 days. From day 16 onward, body weight gain in AOD-9401-treated animals was significantly lower than that of saline-treated controls. Food consumption did not differ between the two groups. Analyses of adipose tissue ex vivo revealed that AOD-9401 significantly reduced lipogenic activity and increased lipolytic activity in this tissue. Increased catabolism was also reflected in an acute increase in energy expenditure and glucose and fat oxidation in ob/ob mice treated with AOD-9401. In addition, AOD-9401 increased in vitro lipolytic activity and decreased lipogenic activity in isolated adipose tissue from obese rodents and humans. Together, these findings indicate that oral administration of AOD-9401 alters lipid metabolism in adipose tissue, resulting in a reduction of weight gain in obese animals. The marked lipolytic and antilipogenic actions of AOD-9401 in human adipose tissues suggest that this small synthetic hGH peptide has potential in the treatment of human obesity.

Analyses of insulin-potentiating fragments of human growth hormone by computative simulation; essential unit for insulin-Involved biological responses

We analyzed the structural features of insulin-potentiating fragments of human growth hormone by computative simulations. The peptides were designated from the N-terminus sequences of the hormone positions at 1–15 (hGH1–15; H2N-Phe1-Pro2-Thr3-Ile4-Pro5-Leu6-Ser7-Arg8-Leu9-Phe10-Asp11-Asn12-Ala13-Met14-Leu15-COOH), 6–13 (hGH6–13), 7–13 (hGH7–13) and 8–13 (hGH8–13), which enhanced insulin-producing hypoglycemia. In these peptide molecules, ionic bonds were predicted to form between 8th-arginyl residue and 11th-aspartic residue, and this intramolecular interaction caused the formation of a macrocyclic structure containing a tetrapeptide Arg8-Leu9-Phe10-Asp11. The peptide positions at 6–10 (hGH6–10), 9–13 (hGH9–13) and 10–13 (hGH10–13) did not lead to a macrocyclic formation in the molecules, and had no effect on the insulin action. Although β-Ala13hGH1–15, in which the 13th-alanine was replaced by a β-alanyl residue, had no effect on insulin-producing hypoglycemia, the macrocyclic region (Arg8-Leu9-Phe10-Asp11) was observed by the computative simulation. An isothermal vibration analysis of both of β-Ala13hGH1–15 and hGH1–15 peptide suggested that β-Ala13hGH1–15 molecule was more flexible than hGH1–15; C-terminal carboxyl group of Leu15 easily accessed to Arg8 and inhibited the ionic bond formation between Arg8 and Asp11 in β-Ala13hGH1–15. The peptide of hGH8–13 dose-dependently enhanced the insulin-involved fatty acid synthesis in rat white adipocytes, and stabilized the C6-NBD-PC (1-acyl-2-[6-[(7-nitro-2,1,3benzoxadiazol-4-yl)amino]-caproyl]-sn-glycero-3-phosphatidylcholine) model membranes. In contrast, hGH9–13 had no effect both on the fatty acid synthesis and the membrane stability. In the same culture conditions as the fatty acid synthesis assay, hGH8–13 had no effect on the transcript levels of glucose transporter isoforms (GLUT 1, 4) and hexokinase isozymes (HK I, II) in rat white adipocytes. Judging from these results we considered that the macrocyclic structure in human growth hormonal peptides is regarded with the modification of insulin action, and hGH8–13 is an essential sequence for the modification of insulin action. This hGH8–13 peptide modifies the insulin action via stabilizing the cell membrane, and does not directly act on the insulin-involved glucose metabolism.

Human growth hormone fragment (hGH44-91) produces insulin resistance and hyperinsulinemia but is less potent than 22 kDa hGH in the rat.

A 17 kDa fragment of human growth hormone (22 kDa hGH), identified as hGH44-191, has lower binding affinity for growth hormone receptors (GHRs), but has been reported to be more potent in producing glucose intolerance in yellow obese mice. Out aim was to investigate this anomaly by comparing acute development of hyperinsulinemia and insulin resistance ("diabetogenic activity") during hGH44-191 or 22 kDa hGH infusion in normal rats. Fasted awake make rats (350-370 g) were infused via a carotid cannula with saline (CON), 22 kDa hGH (at 0.125 micrograms/min), or hGH44-191 (at 0.64 or 0.32 micrograms/min) for 5.75 h. Over the last 2 h, a euglycemic hyperinsulinemic clamp (insulin infusion rate 0.25 U/kg/h) was performed. After 3.75 h infusion, 22 kDa hGH at 0.125 and hGH44-191 at 0.64 micrograms/min produced basal (preclamp) hyperinsulinemia compared to CON. During the clamp, insulin resistance was consistently produced by 22 kDa hGH at 0.125 and hGH44-191, at 0.64 micrograms/min compared to CON. Using specific radioimmunoassays for 22 kDa hGH and hGH44-191, we determined that under conditions of equivalent diabetogenic activity, molar circulating levels of hGH44-191 were 50-60-fold higher than 22 kDa hGH. It was concluded that whereas 22 kDA hGH and hGH44-191 are both capable of generating acute hyperinsulinemia and insulin resistance in the normal rat, the diabetogenic potency of hGH44-191 is not enhanced compared to 22 kDa hGH, and that diabetogenic potency is in accord with the reported lower binding affinity of hGH44-191 to the GHR.

Synthesis of stereoisomers and isoforms of a tryptic heptapeptide fragment of human growth hormone and analysis by reverse-phase HPLC and capillary electrophoresis.

The amino acid sequence Asn-Gly has at pH 7 a tendency to induce deamidation of asparagine to aspartic acid via the formation of a cyclic imide. This imide opens up to yield Asp-Gly or the isoaspartic acid (isoAsp) form, isoAsp-Gly. Both isomers may be found in their L-form or D-form. Like Asn-Gly, the sequence Asp-Gly has a tendency for isomerization and racemization via the formation of a cyclic imide intermediate. When human growth hormone is digested with trypsin, one of the fragments is a heptapeptide (amino acid residues 128-134) containing the amino acid sequence Asp-Gly (amino acid residues 130 and 131). This heptapeptide, as well as stereoisomers and isoforms where L-Asp was replaced by D-Asp, L-isoAsp, D-isoAsp or the L-cyclic imide, respectively, has been synthesized and used as a standard to achieve separation of the five forms by capillary electrophoresis and by reverse-phase HPLC. Capillary electrophoresis analysis was performed in uncoated capillaries by the use of aspartic acid/cyclodextrin buffers at low pH. The elution order of the aspartic-acid-containing heptapeptides was D-Asp, L-Asp, L-isoAsp, D-isoAsp and L-cyclic imide. Reverse-phase HPLC analysis was performed on a C18 column by the use of a shallow acetonitrile gradient in trifluoroacetic acid/water. The elution order was D-isoasp, L-isoASp, L-Asp, D-Asp and L-cyclic imide. Human growth hormone samples were degraded by incubation at high temperature and analyzed for their potential content of isomerization and racemization products. Only L-forms of aspartic acid and isoaspartic acid of the heptapeptide fragment were found.

Human growth hormone fragments 1-43 and 44-191: in vitro somatogenic activity and receptor binding characteristics in human and nonprimate systems

Human growth hormone fragments 1-43 and 44-191: in vitro somatogenic activity and receptor binding characteristics in human and nonprimate systems

Human growth hormone fragments 1-43 and 44-191: in vitro somatogenic activity and receptor binding characteristics in human and nonprimate systems.

Human GH (hGH) fragments 1-43 and 44-191 have potent in vivo effects on glucose homeostasis in rodents but cannot stimulate body growth. To assess the in vitro bioactivity of these hGH fragments we tested their activity against GH-responsive FDC-P1 cell lines expressing full-length human (h), mouse (m), or rabbit (r) GH receptors (GHR). Binding specificity and affinity was tested using GHR-containing membrane preparations from three species and recombinant hGH binding protein (hGHBP). Recombinant hGH 1-43 and recombinant 44-191 stimulated proliferation of FDC-P1-hGHR cells with half-maximal effect at approximately 2000 and 100 nM, respectively, whereas intact hGH stimulates proliferation of FDC-P1-hGHR cells with ED50 of 0.02-0.03 nM. However, these fragments had minimal effect on cells expressing mGHR or rGHR. Although 44-191 did not stimulate proliferation of FDC-P1-rGHR cells, when added to these cells in the presence of 0.23 nM hGH, it antagonized hGH action in a dose-dependent manner (ED50 at 230 nM). Binding of these GH fragments was compared using membrane preparations from rabbit liver, rabbit and mouse adipose tissue, and recombinant hGHBP. Binding competition curves were consistent, with 44-191 having at least a 10-fold lower affinity for rabbit liver GHR and rabbit adipose GHR than bovine GH and a 61-fold lower affinity for hGHBP than hGH. Binding of hGH 1-43 could not be demonstrated to GHRs in rabbit liver microsomes, adipose microsomes, or to hGHBP. HGH 1-43 did not compete for insulin binding sites in adipose microsomes. In conclusion, hGH 44-191 binds with low affinity to the GHR and at supraphysiologic levels stimulates proliferation of FDC-P1-hGHR cells. At high doses, 44-191 can also antagonize GH action in FDC-P1-rGHR cells, presumably by blocking receptor dimerization. Binding of 1-43 to GHR could not be detected, and the basis for its weak in vitro mitogenic effect remains to be elucidated. The low affinity of the fragments for cloned GHRs and low biopotency in these systems suggests that the metabolic actions of these fragments are unlikely to be mediated by the cloned GHR. This raises the possibility of a separate receptor mediating metabolic effects of these fragments.

Synthesis of somatostatin and 31–44 fragment of human growth hormone in escherichia coli

Synthesis of somatostatin and 31–44 fragment of human growth hormone in escherichia coli

Variant forms and fragments of human growth hormone in serum

Variant forms and fragments of human growth hormone in serum

Stimulation of insulin receptor tyrosine kinase activity by an amino terminal sequence of human growth hormone

The in vitro effect of a hypoglycaemic fragment of human growth hormone containing the sequence H 2N-LeuSerArgLeuPheAsu 11AsnAlaCOOH (Asu 11hGH 613) on tyrosine kinase of rat hepatic insulin receptors was examined. Insulin receptor kinase activity was evaluated using the synthetic polypeptide poly(GluTyr) (4:1) as substrate. The hypoglycaemic Asu 11hGH 613 appeared to enhance the phosphorylation of the exogenous substrate by the stimulation of insulin receptor kinase activity. The levels of poly(GluTyr)(4:1) phosphorylation were significantly higher in the insulin receptor preparations incubated in the presence of the Asu 11hGH 6 613 peptide. A dose dependent stimulation of receptor kinase activity was observed and this stimulatory effect was found to be further enhanced by the addition of increasing concentrations of insulin. In hepatic extracts depleted of insulin receptor, no stimulation of kinase activity by the Asu 11hGH 613 was observed. From these data, it is concluded that the increase of poly (GluTyr)(4:1) phosphorylation is the result of the interaction between the Asu 11hGH 613 and the hepatic insulin receptor.

Human growth hormone: 1974-1981.

Chemical investigations of the human growth hormone (HGH) molecule were briefly reviewed for th period between 1974 and 1981. These include chemical modification, selective enzymic cleavage, the 20K HGH, synthetic peptide fragments, complementation of the natural NH2-terminal 134-amino acid fragment with natural or synthetic COOH-terminal fragments of various chain lengths, covalent reconstitution of two contiguous fragments of HGH with thrombin and bacterially synthesized methionyl-HGH.

Method optimization in capillary zone electrophoretic analysis of hGH tryptic digest fragments

The mobile phase composition was optimized for the separation of tryptic digest fragments of human growth hormone by capillary zone electrophoresis. The effect of pH (pH 2.4, 6.1, 8.1 and 10.4) was evaluated since pH determines the relative charge of species, the prime contributor to selectivity; pH 8.1 was selected for the optimization studies. Tricine (buffer), sodium chloride (ionic strength adjustor), and morpholine (mobile phase additive) concentrations were systematically varied at pH 8.1. All three exhibited major effects on the electroosmotic flow velocity and current, and minor effects on selectivity. Tricine was the most crucial for good resolution, although addition of morpholine helped to resolve closely eluting species. The optimum separation conditions were found to be pH 8.1 with 0.1 M tricine, 0.02 M morpholine and no salt.

A comparison of cellular actions between gliclazide and a hypoglycaemic peptide fragment of human growth hormone (hGH 6–13)

The mechanisms of hypoglycaemic action of a 'second-generation' sulphonylurea, gliclazide, and a synthetic human growth hormone fragment, hGH 6-13 (Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala), were compared at the cellular level in rats. Both compounds were shown to be hypoglycaemic in vivo although their molecular structures were totally different. Gliclazide was markedly insulinotropic, as are all hypoglycaemic sulphonylureas, whereas hGH 6-13 had no visible effect on basal levels of plasma insulin. However, in vitro studies with isolated pancreatic islets revealed that hGH 6-13 significantly augmented insulin secretion in the presence of exogenous glucose. One other major difference was that gliclazide had no direct effect on insulin receptor function while the synthetic hGH 6-13 increased the binding of insulin to specific receptors on isolated cells. Results suggested that the human growth hormone fragment hGH 6-13 could be a potential anti-diabetes drug with the ability to potentiate circulating insulin action and to achieve blood glucose normalisation.

The synthetic human growth hormone fragment (32-38) increases glucose uptake in the conscious dog.

hGH32-38 was tested to determine if the peptide could affect hepatic glucose production in the conscious dog under basal conditions (euglycemia) or if it could enhance glucose uptake when hyperglycemia was induced. hGH32-38 (1.6 nmol.kg-1.min-1) or vehicle was infused in a cross-over design study into each of 4 conscious 16 h-fasted dogs for 3 h (0-180 min) following a 40 min control period. At 90 min, plasma glucose was raised to and maintained at 9.4 mmol/l by glucose infusion for 3 h (until 270 min). Neither hGH32-38 nor vehicle infusion had a significant effect on insulin and glucagon levels or on tracer determined [( 3-3H]glucose) glucose production. As a result, neither treatment changed plasma glucose (5.72 +/- 0.17 to 5.78 +/- 0.17 mmol/l with hGH32-38; 5.50 +/- 0.22 to 5.50 +/- 0.17 mmol/l with vehicle). Induction of hyperglycemia (9.4 mmol/l) caused glucagon concentrations to fall similarly to about 50 ng/l with and without hGH32-38. Insulin rose to similar levels in both protocols, yet more glucose was required to maintain the same hyperglycemia with hGH32-38 (135-180 min) (74.9 +/- 12.7 vs 43.7 +/- 7.1 mumol.kg-1.min-1, P less than 0.05). In summary, hGH32-38 significantly increased glucose disposition during hyperglycemia and this effect may be attributed to enhanced insulin action or to an insulin independent action of the peptide.