Fat-Mobilising and Ketogenic Activity of Urine Extracts : Relation to Corticotrophin and Growth Hormone

Chalmers, T. M.; Pawan, G. L. S.; Kekwick, A.

doi:10.1016/s0140-6736(60)92658-1

Cited by 135 publications

(9 citation statements)

References 6 publications

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“…In our patients with congenital generalized lipodystrophy we have neither been able to isolate the fat mobilizing substance of Chalmers et al (1960), nor the insulin antagonist factor of Louis et al (1963). On the other hand we have isolated a heterogeneous small molecular fraction from the urine with an insulin-like activity which produced lipoatrophy in rabbits and mice after a latent period of some weeks, which may point to an immunological process, or a slow acting effect on cerebral transmitters.…”

Section: Discussionmentioning

confidence: 71%

Congenital Generalized Lipodystrophy and Experimental Lipoatrophic Diabetes in Rabbits Treated Successfully With Fenfluramine

Trygstad¹,

Foss²

1977

Acta Endocrinologica

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Lipoatrophic diabetes has been produced in rabbits by injection of a fraction prepared from the urine from patients with congenital generalized lipodystrophy. Both these conditions are considered to be hypothalamic syndromes. The animals, and a patient with congenital generalized lipodystrophy and latent diabetes were treated with the dopamine receptor blocker, pimozide, for 4 and 17 months, respectively. The results were discouraging even though the patient got a daily dose of 16 mg pimozide. Fenfluramine has a lowering effect on brain serotonin, and peripheral effects on glucose and triglyceride metabolism. This drug improved the general condition of the rabbits with lipoatrophic diabetes, as well as that of the patient with congenital generalized lipodystrophy.The rabbits became normoglycaemic and insulin sensitive. In the patient a normalization of the urinary excretion of the serotonin metabolite 5-OH-indole acetic acid was observed.His voracious hunger and profuse perspiration were reduced, the hyperkeratotic layer of the skin peeled off, and the pigmentations of the skin decreased. There was observed an improvement of ALAT and ASAT, normalization of the fasting blood glucose, and increased sensitivity to exogenous insulin. After 11 months of 200 mg fenfluramine daily addtitional administration of 2 g clofibrate per day produced normalization of the serum triglyceride concentration and a marked reduction of the resistance to insulin. Three more patients with congenital generalized lipodystrophy, two of whom have manifest diabetes, have now started

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Section: Discussionmentioning

confidence: 71%

Congenital Generalized Lipodystrophy and Experimental Lipoatrophic Diabetes in Rabbits Treated Successfully With Fenfluramine

Trygstad¹,

Foss²

1977

Acta Endocrinologica

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“…For isolation of the urinary lipodystrophic fraction (LDFr) all steps were carried out at 0-4°C with fresh urine. The alcoholic benzoic acid precipitation, and washings of the precipitate with ethanol were performed according to Chalmers et al (1960). The washed precipitate was dissolved in 0.1 M ammoniumbicarbonate pH 8.5, and the residue was centrifuged off.…”

Section: Methodsmentioning

confidence: 99%

“…In 1947Weil Sc Sletten (1947 isolated an adipokinetic factor from the urine of fasting rabbits. Similar lipolytic substances were prepared from the urine of fasting man (Chalmers et al 1960), rat (Beaton et al 1964), and chicken (Nir et al 1969). Seifter et al (1968) found a "lipid mobilizer" in normal human urine, and Ng et al (1971) isolated a hypoglycaemic "Cataglykin".…”

mentioning

confidence: 99%

Lipoatrophy Produced in Mice and Rabbits by a Fraction Prepared From the Urine From Patients With Congenital Generalized Lipodystrophy

Foss¹,

Trygstad²

1975

Acta Endocrinologica

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Urine from 5 patients with congenital generalized lipodystrophy has been fractionated by protein precipitation and Sephadex gel filtration. A fraction with a molecular weight in the range of 1000 was observed to be metabolically active in mice, rats, and rabbits. Hypophysectomized rats got hypoglycaemia following an injection, and the lipolytic-hyperglycaemic effect of ACTH was reduced after injection into intact mice. This effect was probably due to insulin release, because no insulin-like activity was observed on isolated fat cells in vitro. Persistant changes were observed in the animals after 3 weeks of daily injections of the urinary fraction. Adult mice and rabbits developed lipoatrophy with decrease of body weight in spite of a doubling of the food consumption. The metabolic rate and the body temperature were raised. Infantile animals developed a lipodystrophic state with increased growth velocity, and 50 per cent increase of the body weight, although no fat depots were observed. The treated animals got hyperglycaemia, hypertriglyceridaemia, hyperinsulinaemia, and insulin resistance. The rabbits developed manifest diabetes. The corresponding fraction prepared from the urine from the lipoatrophic rabbits produced lipoatrophy after injection into the mice. It is suggested that the lipodystrophic urinary fraction is of hypothalamic origin, and that it acts through the pituitary gland. The fraction is still heterogenous, and was observed to contain thyrotrophin releasing activity.

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“…More recently, Bornstein & Hyde (1960) have reported the separation, from extracts of human pituitaries, of a peptide with hypoglycaemic but no growth-promoting activity. It cannot be assumed that these hypoglycaemic peptides are similar to peptide 6 isolated in the present work, since the hypo¬ glycaemic peptide described by Chalmers et al (1960) appears to be also of pituitary origin, but differs from peptide 6 in its biological properties. The question of the general occurrence in the anterior pituitary gland of a substance similar to peptide 6 must therefore be left open at present.…”

Section: Discussionmentioning

confidence: 56%

Purification and Properties of a Hypoglycaemic Peptide From Ox Growth Hormone

Huggins¹,

Ottaway²

1961

Journal of Endocrinology

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A peptide has been isolated from crystalline ox growth hormone (GH) which stimulates glucose uptake by isolated rat diaphragm when incubated with it at low concentrations (0\m=.\01\g=m\g./ml.medium). The peptide also causes a slight but persistent hypoglycaemia in fasted mice and rabbits. The increase in glucose uptake by diaphragm is not accompanied by increased glycogen synthesis; in certain circumstances it causes a diminution in lactate output. When incubated with normal rat diaphragm in the absence of acetate, very high concentrations (10 \g=m\g./ml.) cause an inhibition of glucose uptake.The peptide appears to have negligible effects on fat metabolism. The peptide has a mol. wt. of 5,000-10,000, an isoelectric point of about pH 6, and an N-terminal methionine. The amino acid composition is noteworthy for the complete absence of basic amino acids.It is concluded that ox GH freed from this peptide will stimulate glycogen synthesis by muscle without increasing the uptake of glucose.

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Fat-Mobilising and Ketogenic Activity of Urine Extracts : Relation to Corticotrophin and Growth Hormone

Cited by 135 publications

References 6 publications

Congenital Generalized Lipodystrophy and Experimental Lipoatrophic Diabetes in Rabbits Treated Successfully With Fenfluramine

Congenital Generalized Lipodystrophy and Experimental Lipoatrophic Diabetes in Rabbits Treated Successfully With Fenfluramine

Lipoatrophy Produced in Mice and Rabbits by a Fraction Prepared From the Urine From Patients With Congenital Generalized Lipodystrophy

Purification and Properties of a Hypoglycaemic Peptide From Ox Growth Hormone

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