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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 47 (1985), S. 443-467 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 326 (1987), S. 549-549 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] FROESCH AND ZAPF REPLY-Robinson, Clark and Carlsson demonstrate very beautifully that the restoration of normal-glycaemia in diabetic rats by insulin normalizes the secretory pattern of growth hormone. However, we do not agree with their view that the effects of IGF-I on growth simply reflect ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 1. La glycémie, l'insuline immunoréactive et les activités insuliniques supprimable et non supprimable ont été mesurées chez des rats chez les quels une hyperglycémie avait été provoquée par le glucose ou le D-mannoheptulose. Une corrélation entre la glycémie et l'activité insulinique supprimable a été observée dans tous les groupes de rats à l'exception de ceux traités par le mannoheptulose. Ces résultats confirment l'hypothèse selon laquelle l'action hyperglycémiante du mannoheptulose est due à son pouvoir inhibiteur de la sécrétion d'insuline par les cellules B des îlots de Langerhans.-2. Bien que les valeurs des activités insuliniques immunoréactive et supprimable fussent semblables, la corrélation quantitative entre ces deux mesures ne s'est pas avérée satisfaisante.-3. L'activité insulinique non supprimable est restée la même dans tous les groupes de rats. Les fluctuations de l'activité insulinique supprimable ne se sont pas traduites par des fluctuations de la concentration de l'activité insulinique non supprimable.
    Abstract: Zusammenfassung 1. Blutglucose, immunoreaktives Insulin, hemmbare und nicht hemmbare Insulinaktivität (IA) wurden bei Ratten bestimmt, die mit Glucose oder D-Mannoheptulose hyperglykämisch gemacht wurden. Blutglucose und hemmbare IA korrelierten in allen Gruppen mit Ausnahme der mit Mannoheptulose behandelten Ratten. Diese Resultate bestätigen frühere Befunde und Hypothesen, wonach Mannoheptulose die Insulinsekretion derβ-Zellen der Inseln unterdrückt.-2. Obschon sich immunoreaktives Insulin und hemmbare IA in den verschiedenen Gruppen von Ratten ähnlich verhielten, ergab sich keine gute Korrelation zwischen diesen beiden Größen.-3. Die Konzentration der nicht hemmbaren IA war in allen Gruppen von Ratten ungefähr gleich. Die Veränderungen der hemmbaren IA spiegelten sich in der Konzentration der nichthemmbaren IA nicht wieder.
    Notes: Summary 1. Blood glucose, immunoreactive, insulin suppressible and non-suppressible insulin-like activities were determined in rats after the administration of glucose and D-mannoheptulose respectively. The latter caused a marked rise of the blood sugar concentration There was a correlation between blood sugar and suppressible insulin-like activity in all groups of rats except those injected with mannoheptulose. The results support the concept that mannoheptulose acts by inhibiting the release of insulin from theβ-cells of the islets.-2. Immunoreactive insulin roughly paralleled suppressible ILA, but the quantitative correlation between the two was not satisfactory.-3. Nonsuppressible ILA was approximately the same in all groups of rats. Changes in the level of suppressible ILA were not reflected in the concentration of non-suppressible ILA.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Nonsuppressible insulin-like activity ; NSILA-carrier protein ; human serum ; perfused rat heart ; glucose uptake ; hormone binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human serum in a concentration of 10% in the perfusion medium failed to increase glucose uptake by the isolated perfused rat heart, indicating that nonsuppressible insulin-like activity (NSILA) in whole serum was inactive in this system. When NSILA-carrier protein was added to partially purified NSILA-S, its biological activity on the rat heart disappeared. In contrast, the action of insulin was not affected by the presence of NSILA-carrier protein. Binding of125I-labelled NSILA-S to rat heart was inhibited by NSILA-carrier protein.125I-labelled insulin binding was not inhibited. These results support the hypothesis that NSILA-S bound to serum carrier protein is a large molecular compound which does not readily diffuse out of the capillary bed and therefore does not exert insulin-like effects in vivo.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Insulin-like growth factor-I ; insulin-like growth factor-II ; Type 2 (non-insulin-dependent) diabetes mellitus ; insulin resistance ; triglyceride ; cholesterol ; lipoprotein(a)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients. We, therefore, investigated total and fractionated triglyceride and cholesterol levels, lipoprotein(a), non-esterified fatty acid, and apolipoprotein levels in eight Type 2 diabetic patients during five control, five treatment, and three wash-out days. They received a constant diet throughout and daily 2×120 Μg insulin-like growth factor-I/kg s.c. during the treatment period. Fasting total and VLDL-triglyceride, total and LDL-cholesterol control levels were (mean ± SD) 3.1±2.6, 1.3±1.0, 6.3±1.3, and 4.5±1.1 mmol/l and decreased to 1.6±0.8, 0.6±0.4, 5.0±1.0, and 3.5±1.1 mmol/l, respectively, on the last treatment day (p〈0.01). During therapy, fasting lipoprotein(a) levels and the postprandial area under the triglyceride curve decreased by 48±22 and 32±18% of control (p〈0.01), respectively. In conclusion, insulin-like growth factor-I lowered lipid levels in Type 2 diabetic patients directly or indirectly or both because of decreased glucose and insulin levels. Long-term trials would be of interest with respect to the cardiovascular risk in Type 2 diabetes and patients with hyperlipidaemia.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. S179 
    ISSN: 1432-0428
    Keywords: rhIGF I ; lipid metabolism ; anabolism ; energy expenditure ; insulin sensitivity ; non-insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-like growth factor I (IGF I) is an endocrine hormone that mediates most of the effects of pituitary growth hormone. Other important regulatory factors of serum IGF I levels are insulin and nutrition. Most of the circulating IGF I is bound to three IGF binding proteins (BP), mostly IGFBP-3, BP-2 and BP-1. IGF I is also produced by many cells in the body where it exerts autocrine and/or paracrine effects. IGF I has a specific receptor on most cells, the so-called type 1 IGF receptor. When IGF I is administered intravenously as a bolus it leads to acute hypoglycaemia in a similar way to insulin and mainly with the insulin receptor. Chronic administration of IGF I to hypophysectomized or diabetic rats leads to prominent anabolic effects and growth. In this manuscript, metabolic and endocrine effects of recombinant IGF I are discussed. Recombinant IGF I therapy increases energy expenditure and lipid oxidation and decreases proteolysis and protein oxidation. These effects occur despite a partial inhibition of insulin and growth hormone secretion. The therapeutic spectrum of recombinant IGF I, consisting of inhibition of catabolism, stimulation of anabolism, decreases of triglyceride and cholesterol levels and a striking increase in insulin sensitivity, renders IGF I a very interesting, powerful tool for insulin-resistant states such as non-insulin-dependent diabetes mellitus.
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  • 7
    ISSN: 1432-0428
    Keywords: Substrate oxidation ; energy expenditure ; lipolysis ; ketogenesis ; “dawn” phenomenon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27±4 years, BMI 21.8±1.7 kg/m2) were treated with NaCl 0.9% (saline) or IGF-I (8 Μg · kg−1 · h−1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg−1 · day−1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80% (p〈0.02) and C-peptide levels by 78% (p〈0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10±0.43 (saline) to 2.79±0.37 ml · 100ml−1 · min−1 (IGF-I) (p〈0.02). GH-pulse: 10 h after i.v. GH injection serum GH peaked at 40.9±7.4 ng/ml. GH did not influence circulating levels of total IGFI, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702±267 (saline) and 885±236 (IGF-I) to 963±215 (saline) (p〈0.05) and 1815±586 Μmol/l (IGF-I) (p〈0.02), respectively; after 5 h, 3-OH-butyrate rose from 242±234 (saline) and 340±280 (IGF-I) to 678±638 (saline) (p〈0.02) and 1115±578 Μmol/l (IGF-I) (p〈0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44±195 to 300±370 after 20 min (p〈0.03) and to 287±91 nmol · 100 ml−1 · min−1after 120 min (p〈0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Substrate oxidation ; energy expenditure ; lipolysis ; ketogenesis ; “dawn” phenomenon.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27 ± 4 years, BMI 21.8 ± 1.7 kg/m2) were treated with NaCl 0.9 % (saline) or IGF-I (8 μg · kg–1· h–1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg–1· day–1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80 % (p 〈 0.02) and C-peptide levels by 78 % (p 〈 0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10 ± 0.43 (saline) to 2.79 ± 0.37 ml · 100ml–1· min–1 (IGF-I) (p 〈 0.02). GH-pulse: 10 h after i. v. GH injection serum GH peaked at 40.9 ± 7.4 ng/ml. GH did not influence circulating levels of total IGF-I, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702 ± 267 (saline) and 885 ± 236 (IGF-I) to 963 ± 215 (saline) (p 〈 0.05) and 1815 ± 586 μmol/l (IGF-I) (p 〈 0.02), respectively; after 5 h, 3-OH-butyrate rose from 242 ± 234 (saline) and 340 ± 280 (IGF-I) to 678 ± 638 (saline) (p 〈 0.02) and 1115 ± 578 μmol/l (IGF-I) (p 〈 0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44 ± 195 to 300 ± 370 after 20 min (p 〈 0.03) and to 287 ± 91 nmol · 100 ml–1· min–1after 120 min (p 〈 0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased. [Diabetologia (1996) 39: 961–969]
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  • 9
    ISSN: 1432-0428
    Keywords: Spiny mice ; Acomys cahirinus ; pancreas ; IRI ; insulin secretion ; B-cell hyperplasia ; paleβ-granules ; granule-fusion ; two insulins ; insulin biosynthesis ; spontaneous diabetes ; electronmicroscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé En mesurant les taux plasmatiques de glucose et de l'insuline immunoréactive (IRI), le contenu pancréatique en IRI, et en étudiant à l'aide du microscope électronique les pancréas de souris à piquants normoglycémiques à jeun, nourries ou après injection intrapéritonéale de glucose, les résultats suivants ont été obtenus: sans tenir compte du degré de stimulation pancréatique, les animaux des différents groupes d'âge ont pu être classés en deux catégories, soit ceux ayant une concentration basse ou élevée d'IRI plasmatique. Le fait qu'une corrélation entre le poids corporel et la concentration en IRI plasmatique peut être établie chez les animaux adultes, mais non pas chez les jeunes, indique que l'augmentation du poids corporel est plutôt la conséquence que la cause de l'hyperinsulinémie. Par rapport à d'autres espèces de souris normales ou hyperglycémiques, le contenu pancréatique en insuline des souris à piquants était élevé et augmenta progressivement avec l'âge. Aucune corrélation n'a pu être établie entre les taux d'insuline plasmatique et pancréatique. Par rapport au contenu pancréatique, les concentrations plasmatiques en IRI étaient plus basses que celles d'autres souris normoglycémiques ou obèses-hyperglycémiques. Les cellules B de souris à piquants montrent un degré très élevé de granulation. La plupart des granulesβ sont du type pâle et ont une tendance à la fusion et à la confluence. A l'exception d'un animal sur 200, aucun signe morphologique de sécrétion active d'insuline n'a été observé ni chez les animaux nourris ni après stimulation par le glucose. Par contre, l'injection du glucose était suivie de néoformation de granulesβ dans le complexe de Golgi de cellules déjà fortement granulées. — En se basant sur ces résultats, les auteurs postulent l'existence de deux compartiments à insuline dans les cellules B de la souris à piquants normoglycémique. L'un de ces compartiments — quantitativement peu important — serait accessible à la stimulation par le glucose et serait caractérisé par un taux élevé de renouvellement. Le deuxième —quantitativement plus important — serait relativement inaccessible aux stimuli physiologiques et augmenterait avec l'âge. Les résultats obtenus jusqu'ici ne permettent ni la définition fonctionnelle ni anatomique de ces deux compartiments.
    Abstract: Zusammenfassung Die Bestimmung von Plasma Glukose, Plasma immunoreaktivem Insulin (IRI) und Pankreas-IRI sowie die elektronenmikroskopische Untersuchung der Pankreata normoglykämischer Stachelmäuse im Nüchternzustand, nach Fütterung oder nach intrapsritonealer Injektion von Glucose haben folgende Resultate ergeben: Unabhängig vom Stimulationsgrad des Pankreas ließen sich die Tiere aller Altersklassen in zwei Gruppen mit niedriger oder hoher Plasma-IRI-Konzentration aufteilen. Die Tatsache, daß Körpergewicht und Plasma-IRI-Konzentration bei älteren, nicht aber bei jungen Tieren miteinander korrelierten weist darauf hin, daß beschleunigte Gewichtszunahme eher die Konsequenz als die Ursache der relativ erhöhten Insulinkonzenzentrationen war. Der Insulingehalt des Pankreas aller Tiere war gegenüber demjenigen anderer nicht diabetischer Laboratoriumstiere erhöht und stieg mit zunehmendem Alter an. Es bestand keine Korrelation zwischen Plasma Insulin Konzentration und dem Insulingehalt des Pankreas. Im Verhältnis zum letzteren war die Insulinkonzentration im Plasma aller Tiere niedriger als die anderer normaler oder garobob-hyperglykämischer Laboratoriumstiere. Die B-Zellen des Pankreas sämtlicher Tiere enthielten ungewöhnlich vieleβ-Granula. Bei der Mehrzahl der letzteren handelte es sich um sogenannte „helle“ Granula, die zudem eine charakteristische Tendenz zur Fusion und Konfluenz aufwiesen. Mit Ausnahme eines einzigen Tieres (von 200) konnten auch nach Glucose-Stimulation keine morphologischen Hinweise auf aktive Insulinsekretion festgestellt werden. Dagegen war im Golgi-Komplex der bereits stark granulierten Zellen regelmäßig Neubildung von (β-Granula festzustellen. Aufgrund der erhobenen Befunde wird postuliert, daß die B-Zellen normoglykämischer Stachelmäuse zwei Insulinpools enthalten, von denen der kleinere auf Glucose-Stimulation reagiert und eine hohe Umsatzrate hat, wogegen der zweite und quantitativ bedeutendere, auf normale Stimulation nicht oder nur wenig anspricht und mit steigendem Alter zunimmt. Aufgrund der bisher vorliegenden Resultate können diese Pools weder funktionell noch anatomisch definiert werden.
    Notes: Summary Plasma glucose, plasma IRI and pancreatic IRI content were measured and B-cell morphology was studied in fasted, fed and glucose-injected normoglycemic spiny mice of varying ages. Both high and low plasma IRI concentrations were observed at all ages, irrespective of the degree of pancreatic stimulation. In old but not in young animals, plasma IRI concentrations correlated with body weight, suggesting that accelerated weight gain was secondary to hyperinsulinemia. Pancreatic IRI content was higher than in other strains of non-diabetic mice and increased with age but was unrelated to either plasma IRI concentrations, or to body weight individual age groups. Relative to pancreatic IRI content, plasma IRI concentrations of spiny mice were lower than those of normal or obese-hyperglycemic mice of other strains. The B-cells showed an unusual degree of granulation. Pale granules predominated and had a characteristic tendency to fusion and confluence. With the exception of 1 out of 200 animals (in the islets of which emiocytosis was seen), no signs of enhanced insulin release could be observed. Neo-formation ofβ-granules by the Golgi complex of already well granulated cells was the only feature consistently associated with pancreatic stimulation by glucose injection. The data are in agreement with the hypothesis of a B-cell defect resulting in an impairment of insulin secretion and also suggest that the B-cells of normoglycemic spiny mice may contain two compartments of insulin: one which is accessible to secretory stimulation and has a rapid turnover and one which is relatively inaccessible to stimulation and accumulates with age. Available data do not allow for the identification of the postulated defect or for the anatomical or physiological definition of the two compartments of insulin.
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  • 10
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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