Biomedical subjects

F J Ballard

Publications and source records attributed to F J Ballard.

At least 37 records · Page 2Linked to original sources

PubMed1995

Milk-derived growth factors as serum supplements for the growth of fibroblast and epithelial cells.

We have investigated the response of several epithelial and fibroblastic cells to a mitogenic extract of bovine milk. Cation exchange chromatography was used to produce a mitogen-rich fraction from an industrial whey source that, although comprising only 0.5% of total whey protein, contained the bulk of the growth factor activity. This fraction was a source of potent growth promoting activity for all mesodermal-derived cells tested, including human skin and embryonic lung fibroblasts, Balb/c 3T3 fibroblasts, and rat L6 myoblasts. Maximal growth of all these cell types exceeded that observed in 10% fetal bovine serum. Feline kidney and baby hamster fibroblasts and Chinese hamster ovary cells were less responsive, achieving a maximal growth response of 50-75% that observed in 10% fetal bovine serum. Maximal growth achieved in whey-extract-supplemented cultures of Balb/c 3T3 and human skin fibroblasts, and L6 myoblast cultures exceeded that seen in response to recombinant acidic or basic fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, or epidermal growth factor. Importantly, addition of low concentrations of fetal bovine serum to the whey-derived mitogenic fraction produced an additive response. However, concentrated milk-derived factors were found to be inhibitory to the growth of all epithelial lines tested, including rat intestinal epithelial cells, canine kidney epithelial cells, and mink lung cells. It is concluded that industrial whey extracted in this form constitutes an important source of potent growth-promoting agents for the supplementation of mesodermal-derived cell cultures.

3T3 Cells↗

PubMed1995

In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness.

IGF-I analogues that bind poorly to IGFBPs are substantially more potent than IGF-I at stimulating growth in rats. However, rodents differ from other mammals because they contain only minimal circulating levels of IGF-II and they are poorly responsive to GH. In this report we review a series of experiments carried out in pigs, a species that is both GH responsive and has high blood concentrations of IGF-II. Intravenous bolus administration of IGFs to 55 kg pigs depressed blood glucose with the potency greatest for analogues such as des (1-3) IGF-I, R3IGF-I and Long R3IGF-I that showed the weakest binding to pig IGFBP-3, a similar efficacy pattern to that reported in the rat. Chronic subcutaneous administration of Long R3IGF-I, however, reduced growth rates, led to a depression in food intake and lowered concentrations of IGF-I, IGF-II and IGFBP-3. IGF-I itself depressed IGF-II concentrations and did not stimulate growth. Subcutaneous infusion of IGFs over a 3-day period, also in 55 kg pigs, demonstrated that analogues that bound least well to IGFBP-3 were the most effective at reducing the concentration of this binding protein, suggesting that the inhibition of growth was related to the depression of IGFBP-3. On the other hand, IGF-I and Long R3IGF-I increased growth rats in neonatal pigs, especially under conditions of reduced food intake. As these anabolic effects occur at a developmental stage where the animals are insensitive to GH in a manner analogous to the situation in rats, it is plausible that the feed-back inhibition of GH secretion explains the catabolic response to IGFs in older pigs.

Aging↗

PubMed1995

Identification of fibroblast growth factors in bovine cheese whey.

Acidic and basic fibroblast growth factors (FGF) were identified in bovine cheese whey after partial purification using a two step procedure. Cation-exchange chromatography produced a mitogen-rich extract which was loaded on to a heparin-sepharose column and eluted stepwise with 0.8, 1.2 and 2.0 M-NH4HCO3. Mitogenic activity was found in all three fractions by cell growth assays using Balb/c-3T3 fibroblasts. Immunoblotting identified acidic FGF in the 1.2 M-eluate and basic FGF in the 2.0 M-eluate, but neither acidic nor basic FGF was detected in the 0.8 M-fraction. Quantitative radioreceptor assays indicated 5.8 ng of acidic FGF-like activity and 19.8 ng of basic FGF-like activity per 1 whey in the appropriate eluates. This study represents the first direct demonstration of FGF in milk.

3T3 Cells↗

PubMed1995

Production and characterization of recombinant chicken insulin-like growth factor-II from Escherichia coli.

Recombinant chicken (c)IGF-II has been produced in Escherichia coli after first modifying a plasmid that coded for a human (h)IGF-II fusion protein. The cIGF-II fusion protein, deposited in bacterial inclusion bodies, was dissolved under reducing conditions, desalted, subjected to anion-exchange chromatography and refolded. Recombinant cIGF-II was then released from the fusion protein using a genetically engineered serine protease and purified to homogeneity by reverse-phase HPLC. In vitro analysis of recombinant cIGF-II revealed differences between cIGF-II and its human counterpart. Recombinant cIGF-II was less potent than hIGF-II in stimulating protein synthesis in rat myoblasts. This appeared to be due to a decreased affinity for the type-1 IGF receptor. The human and chicken peptides were similar, however, in studies assessing binding to the type-2 IGF receptor and to IGF-binding proteins. Moreover, recombinant cIGF-II and hIGF-II were equipotent in both biological and receptor binding studies in chick embryo fibroblasts, suggesting that there may be a difference between mammalian and avian type-1 IGF receptors.

Amino Acid Sequence↗

PubMed1995

Continuous 14 day infusion of IGF-II increases the growth of normal female rats, but exhibits a lower potency than IGF-I.

The effects of continuous 14 day infusion of recombinant human IGF-I (104 or 260 micrograms/day) or IGF-II (104, 260 or 650 micrograms/day) via s.c. implanted osmotic pumps were compared in young female rats in order to establish the relative efficacies of these two growth factors. Significant increase in body weight gain and feed conversion efficiency were achieved by 260 micrograms/day of IGF-I or 650 micrograms/day of IGF-II. These treatments were associated with increased nitrogen retention and increases in the fractional weights of kidneys, spleen, total gut and individual gut regions. There was an increase in the size of villi and muscularis lining the jejunum, suggesting an increased absorptive capacity of the gut. However there was no significant change in the amount of faecal nitrogen excretion when expressed as a percentage of nitrogen intake. Interestingly, IGF-II was at least as potent as IGF-I in increasing the depth of jejunal crypts. Infusion of equivalent doses of either IGF-I or IGF-II resulted in similar increases in circulating concentrations of the respective peptides, though IGF-II infusion dose-dependently decreased plasma IGF-I concentrations from those of the controls. Plasma IGF-binding protein levels were increased by both IGF-I and IGF-II treatments, though IGF-I elicited greater responses. In summary, IGF-II can promote the growth of young female rats, although generally less potently than IGF-I.

Animals↗

PubMed1995

Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig.

We have tested whether an animal with substantial amounts of both IGF-I and IGF-II in circulation, such as the guinea pig, would respond to chronic IGF infusion in the same manner as the adult rat, which has negligible amounts of IGF-II in blood. Female guinea pigs of 350 g body weight were continuously infused for 7 days with recombinant guinea pig IGF-I or -II (120 or 360 micrograms/day) or long R3 IGF-I (LR3IGF-I) (120 micrograms/day), an analogue which has much reduced affinities for IGF binding proteins. IGF-I or IGF-II infusion led to substantial increases in plasma IGF-I or IGF-II respectively in comparison with vehicle-infused animals. Nevertheless, body weight gain, feed intake, feed conversion efficiency and carcass composition were not significantly affected by any treatment (significance was deemed to be P < 0.05). Amongst the tissues examined only the fractional weight (g/kg body weight) of the adrenals was increased, and that only by the higher dose (360 micrograms/day) of IGF-I. However, the fractional weight of adrenals, gut, kidneys and spleen were significantly increased by LR3IGF-I, but again overall growth was not stimulated. A possible explanation for the lack of IGF-I effects is that total circulating IGF concentrations were not increased by these treatments. IGF-II significantly raised total IGF concentrations at the higher dose only. Plasma IGF-I was reduced by IGF-II infusion, as was plasma IGF-II by IGF-I infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1995

Extraction from cheese whey by cation-exchange chromatography of factors that stimulate the growth of mammalian cells.

Bovine cheese whey was investigated as a source of growth-stimulating factors that might replace or supplement fetal bovine serum in cell culture. Although some cell growth activity was demonstrated in whey or whey ultrafiltrates, enrichment on the basis of molecular size was not useful because the most abundant whey proteins, beta-lactoglobulin and alpha-lactalbumin, have molecular masses that are similar to most known growth factors. Instead, cation-exchange chromatography was selected as an enrichment process because, in contrast to the major whey proteins, growth factors generally have basic isoelectric points. Adsorption to and elution from Sepharose Fast Flow-S resin yielded an extract containing only 1 to 2% of whey protein but substantial growth-promoting activities on Balb/c 3T3 cells, L6 myoblasts, and human skin fibroblasts. The growth activity could be separated from lactoferrin, one of the prominent basic proteins present, through a stepwise elution from the resin. The resultant fraction, which contained lactoperoxidase as the most abundant protein stimulated the growth of the three cell lines at protein concentrations that were 2- to 20-fold lower than observed with fetal bovine serum. Immunoglobulin G could be removed by affinity chromatography, or lactoperoxidase could be inactivated by heat, without significant losses to the growth-promoting capacity of the fraction. These results suggest that enrichment of growth factors by cation-exchange chromatography offers a practical method for the large-scale isolation of an extract from cheese whey that stimulates cell growth.

3T3 Cells↗

PubMed1995

Differences in substrate metabolism between self-perceived 'large-eating' and 'small-eating' women.

OBJECTIVE: To compare different aspects of intermediary metabolism in self perceived 'small-eating' females and self-perceived near normal weight 'large-eating' females and relate the data to those reported for Pima Indians who have the world's highest prevalence of non-insulin dependent diabetes mellitus and obesity. DESIGN: Make repeat measurements of rates of oxygen consumption, carbon dioxide production and blood metabolites in 'large-' and 'small-eating' females at rest, during different activities and after ingestion of a standardised liquid meal. SUBJECTS: Nine self perceived, 'large-eating' females and nine self perceived 'small-eating' females. MEASUREMENTS: Resting metabolic rates (RMR), respiratory quotient (RQ) values and plasma insulin, glucagon insulin-like growth factor (IGF-1), dehydroepiandrosterone sulphate (DHEA-SO4) and glucose. RESULTS: RMR (adjusted for FFM) averaged 3891 +/- 93 J/min in the 'small-eaters' and 3375 +/- 107 J/min in the 'large-eaters' for ten consecutive measurements conducted at 30 min intervals during the control period for the measurement of the thermic effect of food. Over this period the average RQ for the 'small-eating' women (0.81) was significantly greater than that of the 'large-eating' women (0.78). The two groups responded similarly to an oral glucose tolerance test but the concentration of DHEA-SO4 in plasma was 35% higher in the 'small-eaters'. CONCLUSION: The 'small-eating' women may have a greater risk of weight gain but they counteract this tendency by maintaining high activity levels.

Adult↗

PubMed1994

Energy metabolism in free-living, 'large-eating' and 'small-eating' women: studies using 2H2(18)O.

The doubly-labelled water (2H2(18)O) technique was used to assess the long-term rates of energy expenditure and, after accounting for any changes in body composition, the derived rates of energy intake in weight-stable 'large-eating' (n 6) and 'small-eating' (n 6) women. The self-reported energy intakes (approximately 11.2 v. 5.6 MJ/d) and energy expenditures (approximately 8.5 v. 12.4 MJ/d) for the 'large-eating' and 'small-eating' groups respectively, should not be sustainable without significant body-weight changes. 2H2(18)O-assessed rates of energy expenditure for the 'large-eaters' (approximately 8.5 MJ/d) and 'small-eaters' (approximately 11.3 MJ/d) were in close agreement with the results obtained using 5 d, self-reported activity diaries but the derived rates of energy intake for the 'large-' (approximately 8.5 MJ/d) and 'small-eaters' (approximately 10.8 MJ/d) were markedly different from those obtained using self-reported, weighed food diaries. When two 'small-eaters' were supplied with their self-reported energy intakes (approximately 5 MJ/d) for up to 28 d both subjects lost about 0.75 kg body-weight/week. These results provide no support for the existence of 'metabolically efficient' women in the community.

Adult↗

PubMed1994

Cell culture as a tool for identifying nutritional disease therapies.

Cell culture methodologies can be used to help develop therapies for the treatment of polytrauma. An overview is presented of research with the L6 myoblast cell line that led to the discovery of the truncated insulin-like growth factor (IGF) variant, des(1-3)IGF-I and that gave an explanation of the enhanced potency of this growth factor. Subsequent efforts to develop an even more potent variant also utilized cultured cells as indicator bioassays. Such experiments not only provided mechanistic information on IGF action but also directed attention towards IGF variants that were later shown to be more potent in vivo at reversing catabolic conditions.

Animals↗

PubMed1994

Effects of insulin-like growth factor-I peptides in rats with acute renal failure.

The effect of insulin-like growth factor-I (IGF-I) administration on body weight gain and the rate of recovery of renal function was investigated in rats following an acute episode of renal ischaemia. Since the des(1-3)IGF-I and LR3IGF-I variant forms of IGF-I have been shown to be more potent than IGF-I, their effects were also examined. Acute renal failure was produced in male Sprague-Dawley rats by clamping both renal arteries for 45 min. Treatment was commenced at the time of renal artery occlusion with vehicle (0.1 mol acetic acid/l; control group), IGF-I (2.0 mg/kg per day), des(1-3)IGF-I (2.0 mg/kg per day) or LR3IGF-I (1.5 mg/kg per day) by s.c. osmotic pump, and continued for 7 days, with rats being held in metabolism cages. Glomerular filtration rate (GFR) was estimated by the use of 51Cr-EDTA continuously infused i.p. via osmotic pump. Following the episode of renal ischaemia, body weight gain and nitrogen retention were significantly improved in all three peptide-treated groups, and serum urea concentrations were reduced in the groups treated with IGF-I and des(1-3)IGF-I. However, there was no evidence of the variants having any increased potency over the growth effects of IGF-I itself. GFR was significantly reduced, urine output was increased and urinary concentrating ability was reduced in all groups compared with normal rats, with no significant effect of the IGF peptides being apparent. A closer examination of the acute effects of LR3IGF-I on renal function was undertaken by measuring GFR for 3 days before and 3 days after renal ischaemia in two groups of rats, treated for the latter 3 days with either vehicle (controls) or LR3IGF-I (1.5 mg/kg per day). LR3IGF-I treatment following renal ischaemia resulted in a significantly greater fall in GFR than in controls, urinary osmolality was also significantly reduced, and fractional excretion of sodium was increased. In addition, there was histological evidence of a greater degree of tubular epithelial calcification in the kidneys of the rats treated with LR3IGF-I. This study showed that administration of IGF peptides at doses sufficient to cause significant improvement in anabolic status did not improve renal function in rats following an acute episode of renal ischaemia. Indeed the LR3IGF-I variant of IGF-I had a deleterious effect on renal function in the early stage of the recovery period.

Acute Kidney Injury↗

PubMed1994

Differences in the association of insulin-like growth factor-I (IGF-I) and IGF-I variants with rat, sheep, pig, human and chicken plasma-binding proteins.

Associations between labelled insulin-like growth factors (IGFs) and IGF-binding proteins in plasma have been compared in the rat, sheep, human, pig and chicken. The IGFs tested were recombinant human IGF-I, the truncated variant, des(1-3)IGF-I, and LR3IGF-I, an extended form that had been engineered so as to minimize interactions with IGF-binding proteins. Marked species differences were demonstrated, notably that the IGF-I variants which exhibited extremely weak binding in rat plasma bound significantly in plasma from the other species. This result was shown both by size-exclusion chromatography of labelled IGFs added to plasma, in which the extent of variant IGF-I binding decreased in the order sheep > human > pig = chicken > rat, and by competition for labelled IGF-I binding in vitro, in which the order was pig = chicken > sheep > human > rat. Notwithstanding these differences, the two IGF-I variants showed only slight between-species binding differences when tested with purified rat, sheep and human IGF-binding protein-3. Ligand blotting experiments with plasma from the five species similarly showed a consistent pattern in that IGF-I binding was much greater than des(1-3)IGF-I binding, which in turn was greater than LR3IGF-I binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Rapid changes in plasma concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins during anaesthesia in young sheep.

Halothane anaesthesia in young sheep results in greatly increased plasma binding capacity for radiolabelled insulin-like growth factor (IGF), as demonstrated using size-exclusion chromatography. Most of the increased binding was at an estimated molecular mass range of 30-50 kDa, with a smaller increase evident at 130-150 kDa. These changes were not evident in control animals which had food withheld for the same period. The progressive increase in plasma radioligand binding during anaesthesia was the net result of a rise in circulating levels of a 29-31 kDa IGF-binding protein (IGFBP), as shown by ligand blotting, and declining plasma concentrations of IGF-I and IGF-II. Recovery from anaesthesia was accompanied by the restoration of plasma IGFs and the IGFBP towards pre-anaesthesia concentrations. The induced IGFBP was provisionally identified as IGFBP-1 because it bound anti-IGFBP-1 antiserum but not antibodies against IGFBP-2, IGFBP-3 or IGFBP-4. The elevation of plasma IGFBP-1 immunoreactivity was associated with reduced concentrations of glucose and insulin, the regulators of IGFBP-1 in humans and rats. These results suggest that IGF experiments that require anaesthesia but assume that the anaesthetised state is representative of conscious sheep should be reassessed. A similar situation may occur with other mammalian species.

Anesthesia↗

PubMed1994

Transfer of insulin-like growth factor (IGF)-I from blood to intestine: comparison with IGFs that bind poorly to IGF-binding proteins.

The net transfer of 125I-labelled insulin-like growth factor (IGF)-I from the blood to the distal small intestine was measured in anaesthetized lambs using a non-recirculating vascular-perfused intestine. To determine whether IGF-binding proteins (IGFBPs) reduce net IGF transfer, radiolabelled IGF-I was compared with two analogues, des(1-3)IGF-I and LR3IGF-I, which show reduced affinity for IGFBPs. Radiolabelled IGF-I, des(1-3)IGF-I or LR3IGF-I (1 ng/ml plasma) was infused for 45 min into the arterial supply of a 10 cm intestinal segment, either in the absence of added unlabelled peptide (high specific activity) or in the presence of a 100-fold excess of unlabelled homologous peptide (low specific activity) to achieve different proportions of free and complexed peptide. Very little degradation of radiolabelled peptides was detected in plasma, with 3-10% degradation in the intestinal tissue. Less than 5% of radiolabelled IGF-I remained as free peptide in the efferent venous plasma of the perfused segment at both specific activities. Bound radiolabelled IGF-I was found by size-exclusion chromatography mainly in the 30-50 kDa region, with a smaller proportion in the 150 kDa peak. The net intestinal transfer of IGF-I, calculated as the sum of the proportions of infused tracer recovered from intestinal tissue, luminal contents and lymph, was 3.46 +/- 0.22% (S.E.M.) and 3.49 +/- 0.93% when infused at high and low specific activities respectively. The analogues differed from IGF-I with up to ninefold higher concentrations of free radiolabelled peptide in venous plasma of the perfused intestinal segment, and corresponding decreases in binding to the 30-50 kDa binding proteins. Notwithstanding these marked differences in the plasma levels of free peptide, net intestinal transfer was very similar for the three peptides, as was the extent of degradation in the intestinal tissue. The lack of correlation between binding to 30-50 kDa binding proteins and net intestinal transfer suggests that association with 30-50 kDa plasma binding proteins is not a rate-limiting determinant of net IGF transfer to intestinal tissue.

Animals↗

PubMed1994

Treatment with IGF-I peptides improves function of the remnant gut following small bowel resection in rats.

The effects of 7 days' s.c. infusion of 111-700 micrograms/day IGF-I on gut growth and absorptive function were examined in growing rats following removal of 70 or 80% of the jejuno-ileum, and compared with the responses to the analogues, LR3IGF-I and des(1-3)IGF-I, which bind poorly to IGF binding proteins. Administration of 278 micrograms/day IGF-I, LR3IGF-I or des(1-3)IGF-I following 70% jejuno-ileal resection significantly attenuated malabsorption of fat and nitrogen. Responses in rats with 80% resection were less substantial, but a dose-responsive reduction in malabsorption was apparent with LR3IGF-I. Both IGF-I and LR3IGF-I were shown to increase body weight gain and food conversion efficiency in a dose-dependent manner following 80% jejuno-ileal resection. Total gut weight was increased by up to 21%, due predominantly to increased weight of the stomach and proximal small bowel, with the latter effect attributable at least in part to an increased bowel length. LR3IGF-I was more potent than IGF-I at stimulating body weight gain and food conversion efficiency, but its potency advantage on gut absorptive function and small intestinal re-growth was less marked. We conclude that administration of IGF-I peptides improves gastro-intestinal absorptive function following partial gut resection, most likely reflecting, at least in part, an increase in gut absorptive surface area.

Adaptation, Physiological↗

PubMed1993

Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II.

Recombinant insulin-like growth factor-II (IGF-II) and two structural analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were produced to investigate the role of N-terminal residues in binding to IGF-binding proteins (IGFBPs) and hence the biological properties of the modified peptides. The growth factors were modelled on two previously characterized variants of IGF-I, des(1-3)IGF-I and [Arg3]-IGF-I, which both show substantially decreased binding to IGFBPs and were expressed as fusion proteins in Escherichia coli. The biological activities of the corresponding analogues of IGF-I and IGF-II were compared in rat L6 myoblasts and H35B hepatoma cells. In the L6-myoblast protein-synthesis assay, the IGF-II analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were slightly more potent than IGF-II but about 10-fold less potent than IGF-I and 100-fold less potent than the respective IGF-I analogues, des(1-3)IGF-I and [Arg3]IGF-I. In H35 hepatoma cells the anabolic response measured was the inhibition of protein breakdown, and the potency order was insulin >>> [Arg3]-IGF-I > des(1-3)IGF-I > [Arg6]-IGF-II > des(1-6)IGF-II > IGF-I > IGF-II. Binding of the IGFs and their analogues to the type 1 IGF receptor in L6 myoblasts and to the insulin receptor in H35 hepatoma cells did not fully explain the observed anabolic potency differences. Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF. We conclude that the observed anabolic response to each IGF was determined by their relative binding to the competing cell receptor and IGFBP binding sites present.

Amino Acid Sequence↗

PubMed1993

Insulin-like growth factor-I and more potent variants restore growth of diabetic rats without inducing all characteristic insulin effects.

The effects of graded doses of insulin-like growth factor-I (IGF-I) and two variants which bind poorly to IGF-binding proteins were investigated in 160 g streptozotocin-induced diabetic rats. The two variants were the truncated form, des(1-3)IGF-I, and another with arginine at residue 3 and an N-terminal extension, termed LR3-IGF-I. The peptides were infused via mini-osmotic pumps. Reference groups received either vehicle or insulin (30 i.u. per day). Treatment led to a marked dose-dependent increase in growth rate and nitrogen balance. The highest dose (695 micrograms/day) of IGF-I increased body weight by 48.1 +/- 1.7 g/7 days, compared with 11.0 +/- 2.8 g/7 days for the vehicle-treated group. The two variants were 2.5-3 times more potent than IGF-I in restoring growth. The insulin-treated group gained more weight (64.5 +/- 1.6 g/7 days), but the added gain was fat (92.5 +/- 4.8 g of fat/kg carcass wet wt., compared with 32.2 +/- 2.1 for all other groups) rather than protein. All peptides increased muscle protein-synthesis rates and RNA levels by up to 50%, with IGF-I the least potent. These high doses of IGFs did not decrease either the glucosuria or the daily excretion rate of N tau-methyl-histidine (N tau-MH). On the other hand, insulin treatment markedly decreased both glucosuria (from 82.7 +/- 5.4 to 4.5 +/- 3.3 mmol/day) and N tau-MH excretion (from 9.3 +/- 0.3 to 7.1 +/- 0.4 mumol/day per kg). This experiment shows that, although IGF-I and variants can restore growth in diabetic rats, other insulin-dependent metabolic processes in liver, muscle and adipose tissue are not restored.

Animals↗

PubMed1993

No major differences in energy metabolism between matched and unmatched groups of 'large-eating' and 'small-eating' men.

Rates of energy expenditure (J/kg fat-free mass (FFM) per min) in normal weight, 'small-eating' men were compared with those obtained for normal weight (n 8) and underweight (n 5) 'large-eating' men. For the matched groups of 'large-' and 'small-eaters' there were no differences in resting metabolic rate (RMR) measurements but during controlled daily activities there was a small but significant increase (P < 0.05) in energy expenditure in the 'large-eaters'. These results contrast with those obtained for the unmatched groups where energy requirements were about 10% (P < 0.01) higher in the underweight 'large-eaters' at rest but were not different during the more energetic (walking) activities. However, after adjustment for differences in FFM between these two groups, the resting energy expenditures of the 'large-eaters' (82.54 (SE 1.51) J/kg FFM per min) were similar to those of the 'small-eaters' (81.87 (SE 1.51) J/kg FFM per min). Oral temperatures were significantly higher in the matched (0.35-0.65 degrees) and unmatched (0.7-0.9 degrees) 'large-eaters' both at rest and during the different activities, but the thermic effect of food (50 kJ/kg FFM) was one fifth lower (not significant) in both groups of 'large-eaters'. These results provide little evidence for any major metabolic differences between groups of 'large-eating' and 'small-eating' men.

Adult↗