Islet cell function and glucose homeostasis in hypopituitary dwarfism: Synergism between growth hormone and cortisone

Underwood, Louis E.; Brande, J. L. Van den; Antony, Gabor J.; Voina, Sandra; Wyk, Judson J. Van

doi:10.1016/s0022-3476(73)80006-x

Cited by 29 publications

(15 citation statements)

References 20 publications

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“…He had left the thyroid field and was involved, amongst others, in the study of the influence of GH and glucocorticoids on glucose homeostasis in hypopituitary children, using the recently developed radioimmunoassays for GH and insulin [33]. After finishing my clinical training period, having spent much of my time at the Clinical Research Unit performing these studies, much to my delight, I was given the freedom to choose a research topic.…”

Section: The Indirect Action Of Gh On Tissue Growth the Somatomedin mentioning

confidence: 99%

A Personal View on the Early History of the Insulin-Like Growth Factors

Brande¹

1999

Horm Res Paediatr

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Salmon and Daughaday, when trying to set up an in vitro assay for Growth Hormone (GH), failed to obtain a direct effect on sulphate uptake in cartilage of hypophysectomized (hypox) rats. They recognised that this was not the consequence of poor methodology or materials, but an encrypted message from the examined system. They decided to turn around and to try and decipher it. Treatment with GH appeared to render hypox rat serum active in stimulating sulphation in hypox rat cartilage. They proposed that GH induced an intermediary substance, responsible for this biological effect: sulphation factor (SF), later renamed to Somatomedin(s) (SM). This hypothesis met with great criticism and very few took on to study this hypothetical substance. Besides disbelief, slow progress was also due to initial lack of a practical assay and to the failure to find a tissue with enriched concentration from which to extract the activity. From experimental evidence, the concept gradually evolved that SF/SM was insulin-like and might be identical to NSILA (non-suppressible insulin-like activity). This again generated controversy. This characteristic was too far away from the known effects of GH to be readily acceptable as a physiological phenomenon. The subsequent recognition of the distinct characteristics of the receptors for SM/NSILA and insulin, the discovery of the SM/NSILA binding proteins and, much later, a beginning understanding of their interactions, modifications and breakdown, have gradually resolved this apparent contradiction. When the sequence of two NSILA molecules became known, they were named IGF-I and -II. Structural similarity with proinsulin and identity of IGF-I with SM-C and -A were established and it was found that Multiplication Stimulating Activity (MSA), a growth factor isolated from fetal calf serum and subsequently from conditioned media of a rat liver cell line, was the rat equivalent of IGF-II. Structure-function relations could be studied, a quest which is not yet brought to an end. Meanwhile, the endocrine profile of SF/SM had gradually emerged by measuring plasma levels with bioassays. The main determinants were found to be age, body size, GH and the nutritional state. Later, radioimmunoassays were developed, enabling consolidation and detailing of these early observations, and allowing explorations at the tissue level. As another aspect of the endocrine paradigm, in vivo effects of IGFs were studied. The initial demonstration of an effect of crude preparations on longitudinal growth in experimental animals raised heavy scepticism, since the effect might have been an artefact caused by contaminants. It took confirmation with highly purified preparations and biosynthetic IGF-I to ease this concern. Still, not until recent years it was demonstrated, by knocking out the genes, that a true physiological and not a pharmacological effect had been induced previously.When it was found that most tissues produce SMs and are sensitive to their actions, the concept emerged that IGFs may have para- and autocrine fu...

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Section: The Indirect Action Of Gh On Tissue Growth the Somatomedin mentioning

confidence: 99%

A Personal View on the Early History of the Insulin-Like Growth Factors

Brande¹

1999

Horm Res Paediatr

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“…In pituitary dwarfism the insulin secretory response to glucose and arginine is greatly diminished (41, 285). The defect is partially corrected by GH administration, but fu ll correction requires the administration of both GH and cortisone (285).…”

Section: Insulinmentioning

confidence: 99%

The Regulation of Growth by Endocrines

Daughaday¹,

Herington²,

Phillips³

1975

Annu. Rev. Physiol.

107

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Normal growth is the product of a complex interaction among nutrition, .circulating hormones, and changing tissue responsiveness. Although malnutrition is probably the world's most common cause of poor growth, the greatest advances in our understanding of the growth process have come from studies of the function of endocrine factors in normal and disordered growth. Limitations of space have led us to give greatest attention to growth hormone and somatomedin because of the many recent developments in these areas. We have emphasized clinical research in many areas to take advantage of the increases in knowledge that have come from the application of modern immunoassay techniques to growth problems in man. SOMATOMAMMOTROPINSThe importance of the pituitary growth hormone (GH) in the regulation of growth in most vertebrate species is generally accepted. Earlier studies have been extensively reviewed and will not be discussed here (34, SO, 60, Ill, 132, 153,215,222,274,297). ChemistryMajor advances have recently been made in the elucidation of the primary structure of many of the mammalian growth hormones and of the other somatotropic or lactogenic polypeptide hormones. Excellent reviews of these studies have been pre sented (182,184,195,303).Annu. Rev. Physiol. 1975.37:211-244. Downloaded from www.annualreviews.org Access provided by University of California -San Francisco UCSF on 02/08/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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“…In both groups with growth hormone deficiency (isolated G H deficiency and panhypopituitarism) and in the group with anorexia nervosa, plasma IRG responses to arginine were slightly higher than in normal children; however, the differences were not effects of growth hormone on insulin secretion have been reported. In children with growth hormone deficiency, plasma IRI responses to arginine (8,41,46,50,51) or to glucose (47) have been reported as either normal or decreased. The mean plasma IRI responses to arginine in the groups with isolated growth hormone deficiency and panhypopituitarism were significantly decreased; however, there was a great individual variation, some subjects exhibiting a normal insulin response.…”

Section: Plasma Immunoreactive Insulin (Iri) (mentioning

confidence: 99%

Plasma Growth Hormone, Insulin, and Glucagon Responses to Arginine Infusion in Children and Adolescents with Idiopathic Short Stature, Isolated Growth Hormone Deficiency, Panhypopituitarism, and Anorexia Nervosa

et al. 1975

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ExtractThe effects of intravenous infusion of arginine (20 g/m2) after an overnight fast on plasma immunoreactive growth hormone (GH), insulin (IRI), and glucagon (IRG), and blood glucose were examined in five groups of children and adolescents: 10 normal individuals, 18 with idiopathic short stature, 6 with isolated growth hormone deficiency, 8 with panhypopituitarism, and 6 with anorexia nervosa.The mean fasting plasma GH concentration was significantly elevated in the group with anorexia nervosa (P < 0.05), and similar to the value for the normal group in all other groups. After arginine infusion, four-to sixfold increases of plasma G H were observed in the normal children, and similar increases were seen in those with idiopathic short stature as well as in those with anorexia nervosa; whereas, in the children with isolated growth hormone deficiency or panhypopituitarism, there was no significant increase in plasma GH. Fasting blood glucose concentrations were significantly lower than normal in subjects with isolated growth hormone deficiency ( P < 0.05), panhypopituitarism ( P < 0.001), and anorexia nervosa (P < 0.001), whereas fasting plasma IRI and IRG concentrations were similar to the values in the normal group. Plasma IRI increased eightfold at the end of the 30-min arginine infusion in the normal subjects; the increase was slightly but not significantly less in those with idiopathic short stature, and significantly less in those with isolated growth hormone deficiency ( P < 0.05), panhypopituitarism ( P < 0.001), and anorexia nervosa ( P < 0.05). Arginine infusion resulted in two-to threefold increases of plasma IRG in the normal group, and similar increases were observed in all of the other groups tested. These results suggest that whereas pancreatic P cell responsiveness may be deficient in children and adolescents with isolated growth hormone deficiency, panhypopituitarism, or anorexia nervosa, pancreatic a cell responsiveness, to arginine a t least, appears to be intact under these conditions. SpeculationAlthough plasma glucagon responses to arginine infusion were not less in subjects with hypopituitarism or anorexia nervosa than in normal subjects, relative hypoglucagonemia may have existed, since both basal and postarginine infusion plasma glucagon levels were not higher than normal in the presence of significantly lower blood glucose values. Thus, the present study does not exclude a deficient pancreatic a cell response to hypoglycemia. Alternatively, nonavailability of substrates for gluconeogenesis may have a more important influence than hormonal factors in the genesis of the hypoglycenia observed in these states.73

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Islet cell function and glucose homeostasis in hypopituitary dwarfism: Synergism between growth hormone and cortisone

Cited by 29 publications

References 20 publications

A Personal View on the Early History of the Insulin-Like Growth Factors

A Personal View on the Early History of the Insulin-Like Growth Factors

The Regulation of Growth by Endocrines

Plasma Growth Hormone, Insulin, and Glucagon Responses to Arginine Infusion in Children and Adolescents with Idiopathic Short Stature, Isolated Growth Hormone Deficiency, Panhypopituitarism, and Anorexia Nervosa

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