Effect of increasing doses of recombinant human insulin-like growth factor-I on glucose, lipid, and leucine metabolism in man.

Turkalj, Igor; Keller, Ulrich; Ninnis, Ronald; Vosmeer, S.; Stauffacher, Werner

doi:10.1210/jcem.75.5.1430077

Cited by 60 publications

(50 citation statements)

References 32 publications

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“…In vitro and in vivo studies have shown that IGF-I is able to influence glucose, amino acid, and lipid metabolism (13)(14)(15), particularly by stimulating transport and utilization of glucose and amino acids and by promoting an overall positive protein balance through activation of protein synthesis and suppression of protein degradation (16,17).…”

Section: Introductionmentioning

confidence: 99%

Divergent Effects of Short‐Term, Very‐Low‐Calorie Diet on Insulin‐Like Growth Factor‐I and Insulin‐Like Growth Factor Binding Protein‐3 Serum Concentrations in Premenopausal Women with Obesity

et al. 1998

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DE PERGOLA, GIOVANNI, MAURO ZAMBONI, NICOLA PANNACCIULLI, EMANUELA TURCATO, FRANCESCO GIORGINO, FABIO ARMELLINI, FRANCESCO LOGOLUSO, MARCELLO SCIARAFFIA, OTTAVIO BOSELLO, RICCARDO GIORGINO. Divergent effects of short-term, very-low-calorie diet on insulinlike growth factor-I and insulin-like growth factor binding protein-3 serum concentrations in premenopausal women with obesity. Obes Res. 1998;6:408-415. Objective: Insulin-like growth factor-I (IGF-I) and insulinlike growth factor binding protein-3 (IGFBP-3) serum concentrations provide a good measure of the biological effects of growt~hormone. The aims of the present study were to: (I) investigate the associations of IGF-I and IGFBP-3 with body fat mass and distribution, and (2) evaluate the effects of 3 weeks of very-low-calorie diet (VLCD) (318 kcal/day, with 40 g protein, 35 g carbohydrate, and 2 g fat) on IGF-I and IGFBP-3 serum concentrations. Research Methods and Procedures:The study was performed in 21 nondiabetic premenopausal women with obesity (body mass index >27.0 kg/rrr'; age: ranging from 18 to 48 years). Body fat mass and distribution were measured by computed tomography.

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Section: Introductionmentioning

confidence: 99%

Divergent Effects of Short‐Term, Very‐Low‐Calorie Diet on Insulin‐Like Growth Factor‐I and Insulin‐Like Growth Factor Binding Protein‐3 Serum Concentrations in Premenopausal Women with Obesity

et al. 1998

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“…Previous studies have investigated the effects of IGF-I infusion on glucose and protein metabolism in healthy subjects (2,4,7,(19)(20)(21). These studies have demonstrated that although large doses of intravenous IGF-I have effects similar to insulin on glucose metabolism, the effects on protein metabolism are different and are characterized by reductions in circulating amino acid concentrations and whole-body protein flux (19), resulting in a direct stimulation of protein synthesis only when amino acid concentrations are maintained (2).…”

Section: Type 1 Diabetes Is Associated With Abnormalities Of the Growmentioning

confidence: 99%

“…Previous studies investigating the effects of IGF-I administration on NEFA metabolism have produced conflicting results, with decreased (19,20,41,42), increased, and unaltered (2,35) plasma NEFA levels reported by various investigators. It is likely that decreased GH-mediated lipolysis and simultaneously enhanced insulin sensitivity resulted in the lower circulating NEFA levels during the IGF-I administration.…”

mentioning

confidence: 99%

IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.

et al. 2000

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Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 µg · kg -1 · day -1 ) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemiceuglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1- 13C]leucine and [6-6-2 H 2 ]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26 ± 0.07 vs. 0.17 ± 0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (~67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37 ± 6 vs. 52 ± 10 µmol · kg -1 · min -1 , P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (~28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17 ± 0.03 vs. -0.10 ± 0.02, P < 0.01, and 0.25 ± 0.08 vs. 0.40 ± 0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulinstimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes. Diabetes 49:789-796, 2000 I GF-I shares a 40% sequence homology with human proinsulin and exhibits both insulin-like and anabolic effects (1,2). The availability of recombinant human IGF-I (rhIGF-I) has led to interest in the potential of this peptide in the treatment of a variety of disease states (3-7). Type 1 diabetes has received particular attention, because the relative portal insulin deficiency of this condition is thought to be responsible for the reduced circulating levels of IGF-I (8), which in turn, through decreased negative feedback, leads to increased secretion of growth hormone (GH) (9).Recent studies have demonstrated improved glycemic control in patients with types 1 and 2 diabetes after IGF-I treatment (10,11). IGF-I administration has also been shown to reduce the GH hypersecretion of adolescents and adults with type 1 diabetes (12,13). In those studies, the reductions in GH secretion were associated with decreased insulin requirements, without alteration in glycemic control, which indicates an increase in insulin sensitivity.In addition to disordered glucose metabolism, patients with t...

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“…The differences between the groups were significant on days 2-6 (*P<0·001). Previous studies of IGF-I in non-traumatised animals and humans have shown that the peptide has a potent hypoglycaemic effect, despite a reducing effect on pancreatic islet -cell secretion (Boulware et al 1992, Mauras et al 1992, Turkajl et al 1992, Elahi et al 1993. In the present study a reduction in postoperative hyperglycaemia was seen in catabolic patients after major operation.…”

Section: Figure 1 Serum Concentrations Of Igf-i In Patients Given Igfmentioning

confidence: 99%

“…Supplementation with insulin-like growth factor-I (IGF-I), the proposed mediator of GH's somatotrophic actions in vivo, was recently shown to reduce nitrogen excretion after surgery and to improve nitrogen balance in healthy human volunteers (Clemmons et al 1992, Leinsköld et al 1995. Other studies in humans have demonstrated that IGF-I exerts insulin-like effects on glucose metabolism (Boulware et al 1992, Turkajl et al 1992. When administered at pharmacological doses, IGF-I reduces circulating insulin levels and exerts a hypoglycaemic effect (Guler et al 1987, Elahi et al 1993, Leinsköld et al 1995.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal growth factors and pancreatic islet hormones during postoperative IGF-I supplementation in man

Leinsköld

Adrian²,

Arnelo³

et al. 2000

Journal of Endocrinology

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Insulin-like growth factor-I (IGF-I) has been demonstrated to exert a nitrogen sparing effect, both experimentally and in patients after abdominal surgery. IGF-I is a major mediator for the anabolic effects of growth hormone (GH). Whether elevated circulating IGF-I levels are the sole mediator of the anabolic effects following GH has not been clarified. IGF-I influences glucose metabolism, both through its own specific receptor and by activating the insulin receptor, and has also been proposed to influence pancreatic islet secretion directly. In the present study, the postoperative effects of IGF-I on plasma levels of other gastrointestinal and pancreatic islet hormones and growth factors were measured in patients after abdominal surgery.Fifteen patients who were candidates for large bowel resection were randomly divided into two groups: IGF-Itreated (n=8) and placebo-treated (n=7). The IGF-I group received daily two s.c. injections of human recombinant IGF-I (80 µg/kg body weight) for five days, beginning on the morning of the first postoperative day. The other group received placebo injections. Fasting plasma levels of gastrointestinal growth factors (epidermal growth factor, transforming growth factor-, IGF-II), gastrointestinal hormones (gastrin, enteroglucagon, peptide YY), and islet hormones (insulin, islet amyloid polypeptide (IAPP) and pancreatic glucagon) were determined by RIA preoperatively and after five days of treatment.No significant effects of IGF-I on other growth factors or gastrointestinal hormones were seen. A marked increase in plasma insulin postoperatively compared with the preoperative levels (42 3 vs 61 5 pM, P<0·05) was seen in the placebo group, whereas the postoperative levels in the IGF-I-treated patients remained unchanged (44 3 vs 45 4 pM). A similar pattern was observed for IAPP and cortisol concentrations. No differences in glucagon concentrations were seen.In conclusion, these results suggest that IGF-I does not influence production of other gastrointestinal hormones thought to be involved in alimentary growth or pancreatic glucagon. In contrast, IGF-I caused a marked reduction of insulin and IAPP secretion. The inhibition of -cell secretion could be direct or, alternatively, could involve an improvement in postoperative insulin resistance, perhaps by reducing serum cortisol.

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Effect of increasing doses of recombinant human insulin-like growth factor-I on glucose, lipid, and leucine metabolism in man.

Cited by 60 publications

References 32 publications

Divergent Effects of Short‐Term, Very‐Low‐Calorie Diet on Insulin‐Like Growth Factor‐I and Insulin‐Like Growth Factor Binding Protein‐3 Serum Concentrations in Premenopausal Women with Obesity

Divergent Effects of Short‐Term, Very‐Low‐Calorie Diet on Insulin‐Like Growth Factor‐I and Insulin‐Like Growth Factor Binding Protein‐3 Serum Concentrations in Premenopausal Women with Obesity

IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.

Gastrointestinal growth factors and pancreatic islet hormones during postoperative IGF-I supplementation in man

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