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

Wade, John D.; Ng, Frank M; Börnstein, J.; Pullin, C. O.; Pearce, John

doi:10.1530/acta.0.1010010

Cited by 5 publications

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“…There was no significant change in circulating levels of blood glucose following a bolus intravenous injection of AOD9401 (250 1000 µg/kg) to the animals (Table 3). Although animals showed a small acute response to AOD9401 at 1000 µg/kg, the highest dose tested in this study, the hyperglycaemic effect of AOD9401 was only marginal (0·6 0·3 vs 0·1 0·2 mM, 30 min after administration) and quickly returned to basal levels within 3 h. These observations were different from those reported in previous studies (Ng & Bornstein 1978, Wade et al 1982. The difference was probably due to the purity of the peptide preparations.…”

Section: Acute Effect Of Aod9401 On Basal Blood Glucose Of Zucker Ratscontrasting

confidence: 99%

Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats

Jiang²,

Gianello³

et al. 2000

Journal of Molecular Endocrinology

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A lipolytic domain (AOD9401) of human growth hormone (hGH) which resides in the carboxyl terminus of the molecule and contains the amino acid residues 177-191, has been synthesized using solid-phase peptide synthesis techniques. AOD9401 stimulated hormone-sensitive lipase and inhibited acetyl coenzyme A carboxylase (acetyl CoA carboxylase) in isolated rat adipose tissues, in a similar manner to the actions of the intact hGH molecule. The synthetic lipolytic domain mimicked the effect of the intact growth hormone on diacylglycerol release in adipocytes. Chronic treatment of obese Zucker rats with AOD9401 for 20 days reduced the body weight gain of the animals, and the average cell size of the adipocytes of the treated animals decreased from 110 to 80 µm in diameter. Unlike hGH, synthetic AOD9401 did not induce insulin resistance or glucose intolerance in the laboratory animals after chronic treatment. The results suggest that AOD9401 has the potential to be developed into a therapeutic agent for the control of obesity.

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Section: Acute Effect Of Aod9401 On Basal Blood Glucose Of Zucker Ratscontrasting

confidence: 99%

Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats

Jiang²,

Gianello³

et al. 2000

Journal of Molecular Endocrinology

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“…Late anti-insulin activities include hyperglycemia (29), hyperinsulinemia (4), increased lipolysis (36,47), decreased glucose transport (48), increased serum nonesterified fatty acids (55), de- creased glucose metabolism (3), and insulin resistance (38,84,85). To explain these two related but opposite activities, as well as the other diverse activities of GH, three hypotheses have been advanced: (1) the existence of multiple GH receptors (31,89,90,121); (2) the presence of multiple "active centers" in the GH molecule (70); and (3) the presence of small, active fragments that result in the multiple activities of GH (5, 99,100,130). Studies continue to test these three hypotheses.…”

Section: Multiple Activities Of Growth Hormonementioning

confidence: 99%

“…Although most were found to be artifacts of experimental manipulation ( l o ) , several studies of such GH fragments have been conducted. For example, hGH 1-15 was found to possess insulinlike activity (5,98-loo), while hGH 177-191 had antiinsulin activity (130,131). In 1988, Salem (118) showed that an hGH amino-terminal peptide, 1-43, was an insulin potentiator that increased insulinstimulated glucose clearance and glucose metabolism without affecting insulin secretion.…”

Section: Multiple Activities Of Growth Hormonementioning

confidence: 99%

Structure‐Function Relationships of Growth Hormone and Other Members of the Growth Hormone Gene Family

Kopchick

Chen

1999

Comprehensive Physiology

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The sections in this article are: Studies Using Growth Hormone Fragments Multiple Activities of Growth Hormone Crystal Structure Studies Regarding Disulfide Bonds Homologue/Alanine Scanning as A Means of Defining Biologically Active Domains The Third α‐Helix Mutagenesis of the Growth Hormone Gene Encoding α‐Helix 3 and Transgenic Mouse Studies Importance of the Amphiphilicity of the Third α‐Helix Designing a Growth Hormone Analogue with a Perfect Amphiphilic α‐Helix Systematic Substitution Mutations in the Hydrophilic Region of the Third α‐Helix of Bovine Growth Hormone Growth Hormone Antagonists Pegylated Growth Hormone Antagonists as Therapeutic Agents Finding of One Growth Hormone/Two Growth Hormone‐Binding Proteins Mutagenesis Studies on the Prolactin Gene Concluding Remarks

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“…Some recent reports have indicated that the amino-terminal fragments of hGH showed an insulin-potentiating action (9)(10)(11)(12)(13)(14)(15)(16), while the carboxyl terminus was antagonistic to insulin action (17). Recent studies with an amino-terminal portion of hGH (hGH1-43) have shown that it enhances insulin action on adipose tissue from obese mice and diabetic rats and potentiates the action of insulin on glucose clearance (1 1, [13][14][15][16].…”

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confidence: 99%

Effects of Hypophysectomy and the Insulin-Like and Anti-Insulin Pituitary Peptides on Carbohydrate Metabolism in Yellow Avy/A (BALB/c x VY)F1 Hybrid Mice

Salem¹,

Lewis²,

Haro³

et al. 1989

Experimental Biology and Medicine

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The amino-terminal portion of human growth hormone, residues 1-43 (hGHi-43), has insulin-potentiating action, while a hyperglycemic pituitary peptide (HP), which co-purifies with human growth hormone (hGH), is antagonistic to the action Of insulin. The effects of hGH, hGHi-43, and HP on glucose metabolism were assessed in young (4-5 weeks) and adult (6-8 months) hypophysectomized yellow AvY/A mice which lacked any interfering endogenous pituitary hormones, and compared with age-matched intact obese yellow AYY/A and lean agouti A/a mice. Treatment with hGH1-43 or HP did not promote body growth in hypophysectomized yellow mice; but after 2 weeks of treatment with hGH, there was a significant increase in body weight (P e 0.05). Treatment with HP raised blood glucose and lowered insulin concentrations in obese yellow mice, but not in agouti or hypophysectomized yellow mice. The severely impaired glucose tolerance of the hypophysectomized yellow mice was improved by acute (60 min) and chronic (3 days) treatment with hGH, -, , as well as by 2 weeks of treatment with hGH; in contrast, HP had no effect. Glucose oxidation in adipose tissue from obese yellow mice was low and showed essentially no response to stimulation by insulin at doses lower than 1000 microunits/ml. Basal glucose oxidation rates in adipose tissue taken from agouti and hypophysectomized yellow mice were significantly higher (P < 0.001) than those in tissue from obese yellow mice, and the rates responded significantly (P < 0.05) to 100 microunits/ml insulin. The insulin binding affinities in liver membranes from agouti mice were higher than those from either obese or hypophysectomized yellow mice. The insulin receptor densities were similar in both agouti and obese yellow mice, but higher in hypophysectomized yellow mice (P e 0.05). Treatment with hGHi-43 slightly increased, although not significantly, the insulin receptor density in yellow obese mice while hGH showed essentially no change. Therefore, hypophysectomy appeared to increase tissue response and decrease insulin resistance by increasing receptor numbers and lowering the circulating insulin levels. Furthermore, the insulin-like action of hGH was elicited directly in vivo by hGHi-43 in hypophysectomized yellow mice. [P.S.E.B.M. 1989[P.S.E.B.M. , Vol 1911 T T u m a n growth hormone (hGH or hGH22k) is known to promote body growth and to show H insulin-like and anti-insulin actions in rodents.

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

Cited by 5 publications

References 0 publications

Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats

Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats

Structure‐Function Relationships of Growth Hormone and Other Members of the Growth Hormone Gene Family

Effects of Hypophysectomy and the Insulin-Like and Anti-Insulin Pituitary Peptides on Carbohydrate Metabolism in Yellow Avy/A (BALB/c x VY)F1 Hybrid Mice

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