The effects of infusion of insulinlike growth factor (IGF) I, IGF-II, and insulin on glucose and protein metabolism in fasted lambs.

Douglas, Richard; Gluckman, Peter D.; Ball, K. T.; Breier, Bernhard H.; Shaw, James H.

doi:10.1172/jci115346

Cited by 139 publications

(77 citation statements)

References 42 publications

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“…In both studies, this important stimulus of nutrient intake was evident in the increased circulating IGF-I during the 24-h period in all feeding groups. Few studies have measured a specific effect of IGF-I on protein synthesis in neonatal animals, although administration of IGF-I has been shown to increase muscle protein synthesis in young growing animals (10,11). Recently, we have demonstrated that chronic administration of IGF-I to neonatal pigs via osmotic pumps resulted in a modest increase in skeletal muscle, but not visceral organ protein synthesis (24).…”

Section: Discussionmentioning

confidence: 99%

Nutrient-Independent and Nutrient-Dependent Factors Stimulate Protein Synthesis in Colostrum-Fed Newborn Pigs

et al. 1995

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Section: Discussionmentioning

confidence: 99%

Nutrient-Independent and Nutrient-Dependent Factors Stimulate Protein Synthesis in Colostrum-Fed Newborn Pigs

et al. 1995

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“…In other IGF-II-transgenic mouse models increased levels of IGFBP-2 (Rogler et al 1994, Wolf et al 1994, IGFBP-1 and IGFBP-5 have been noted (Rogler et al 1994). A drop in the serum level of IGF-I has often been observed after IGF-II administration or IGF-II overproduction (Douglas et al 1991, Koea et al 1992, Rogler et al 1994, Conlon et al 1995, Wolf et al 1995. The reduction in serum IGF-I is most likely due to displacement of IGF-I from the binding proteins in the presence of high concentrations of IGF-II (Blackburn et al 1997).…”

Section: Dexamethasone In Igf-ii-transgenic Mice · R Rooman and Othermentioning

confidence: 99%

The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice

Rooman¹,

Köster²,

Bloemen³

et al. 1999

Journal of Endocrinology

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The physiological role of IGF-II remains unclear but there is evidence for a role in postnatal growth, the growth of the thymus and bone homeostasis. Glucocorticoids have many effects that are opposite to the effects of IGF-II such as growth retardation, osteoporosis and thymic involution. We therefore wondered whether IGF-II overexpression in transgenic mice might counteract some of the growth inhibitory effects of the glucocorticoid, dexamethasone (DXM).In a dose-finding study in normal mice, 20 µg DXM/ day caused a significant growth delay. The various organs had a different susceptibility to the growth inhibitory effects of DXM. Most affected were thymus and spleen, followed by liver, skeletal muscle and lumbar vertebrae. The weights of the kidney, tibia, and humerus were not significantly diminished.In a second experiment, the effects of DXM in normal and IGF-II-transgenic animals were compared. The IGF-II serum levels in the transgenic animals were more than 40-fold increased compared with control mice and were decreased by 35% in the DXM-treated group. IGF-I serum levels were identical in both mouse strains and rose slightly after DXM administration in controls. Transgenic mice had higher levels of IGF binding protein species of apparent molecular masses of 41·5 kDa, 30 kDa, and 26·5 kDa. DXM reduced the 24 kDa band in both mice strains. In addition it reduced the bands at 38·5 kDa and 26·5 kDa but only in the transgenic animals.The effect of DXM on body growth was similar in normal and IGF-II-transgenic mice. The weight reduction of the various organs caused by DXM was similar in both types of mice except for the skeleton. The weight of the tibia and the humerus were significantly higher in the DXM-treated transgenic mice.In conclusion, we speculate that overexpression of IGF-II in mice partially protects bone from the osteopenic effects of glucocorticoids.

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“…On the basis of the observation that co-infusion of IGF-II with IGF-I blocked the anti-catabolic effect of IGF-I in sheep (25), it has been speculated that IGF-II may be a functional inhibitor of IGF-I, representing a mechanism that prevents overgrowth and hyperanabolism (6). Another feature compatible with this hypothesis is the consistently observed decrease in serum IGF-I after administration of IGF-II to pituitary-sufficient animals (14) and in patients (26) or experimental animals (15) …”

Section: Discussionmentioning

confidence: 99%

“…13). Specifically, this approach aimed at elucidating the mechanism of the decrease in serum IGF-I concentrations that is a consistent feature of in vivo studies involving administration of IGF-II to pituitary-sufficient animals (14) or transplantation of IGF-II-secreting tumours to nude rodents (15).…”

Section: Introductionmentioning

confidence: 99%

Interactions of insulin-like growth factor (IGF)-II and growth hormone in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice

Blackburn

Dressendorfer²,

Blum³

et al. 1997

European Journal of Endocrinology

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To study interactions between insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo, we crossed hemizygous transgenic mice carrying phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II fusion genes with hemizygous PEPCK-bovine GH (bGH) transgenic mice. Offspring harbouring both transgenes (IB), the IGF-II transgene (I) or the bGH transgene (B), and non-transgenic littermates (C) were obtained. Blood samples were taken before (end of week 12) and after (end of week 14) the mice had received a diet high in protein and low in carbohydrates to stimulate PEPCK promoter-controlled transgene expression. Mean serum GH concentrations of both B and IB mice corresponded to 900 ng/ml and increased more than twofold (P < 0.001) after 1 week of the high-protein diet. GH concentrations in controls and I mice were less than 20 ng/ml. Serum IGF-II concentrations in I and IB mice were three-to fourfold higher than those in C and B mice. Whereas IGF-II concentrations were not changed by the high-protein diet in the last two groups, serum IGF-II increased significantly in I (P < 0.001) and IB mice (P < 0.05). This increase was significantly (P < 0.05) less pronounced in IB than in I mice. Circulating IGF-I concentrations were about twofold (P < 0.001) higher in B and IB than in C and I mice, and showed a tendency to be lower in I than in C and in IB than in B mice when animals were maintained on the standard diet. The high-protein diet did not change circulating IGF-I concentrations in controls and B mice, but resulted in a significant reduction of serum IGF-I concentrations in I (P < 0.05) and IB mice (P < 0.001). Consequently, after PEPCK-IGF-II transgene expression was stimulated, serum IGF-I concentrations were significantly (P < 0.05) lower in I than in C and in IB than in B mice. Serum IGF-binding protein (IGFBP)-2 concentrations were significantly (P < 0:05) higher in I mice than in all other groups when mice were maintained on the standard diet, with a tendency to reduced IGFBP-2 concentrations in B mice. After the high-protein diet, serum IGFBP-2 concentrations did not change in C and I mice, but increased by two-to threefold in B and IB mice (P < 0:001). Serum IGFBP-3 concentrations tended to be greater in B and IB than in C and I mice, but these differences were mostly not significant. IGFBP-4 concentrations were significantly (P < 0:001) increased by GH overproduction in B and IB mice. Our data suggest that the reduction in circulating IGF-I concentrations by increased IGF-II is most probably due to the limited serum IGF binding capacity and the short half-life of free IGFs, rather than to a reduction in GH-dependent IGF-I production. Effects of GH overproduction on serum IGFBP-2 concentrations depend on dietary factors and may be both inhibitory and stimulatory. European Journal of Endocrinology 137 701-708

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The effects of infusion of insulinlike growth factor (IGF) I, IGF-II, and insulin on glucose and protein metabolism in fasted lambs.

Cited by 139 publications

References 42 publications

Nutrient-Independent and Nutrient-Dependent Factors Stimulate Protein Synthesis in Colostrum-Fed Newborn Pigs

Nutrient-Independent and Nutrient-Dependent Factors Stimulate Protein Synthesis in Colostrum-Fed Newborn Pigs

The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice

Interactions of insulin-like growth factor (IGF)-II and growth hormone in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice

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