Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A

1994 ◽  
Vol 131 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Peter D Zenobi ◽  
Yvonne Glatz ◽  
Annamarie Keller ◽  
Susanne Graf ◽  
Silvia E Jaeggi-Groisman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Type A ◽  
Metabolic Effects ◽  
Insulin Like Growth Factor ◽  
Severe Insulin Resistance ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Zenobi PD, Glatz Y, Keller A, Graf S, Jaeggi-Groisman SE, Riesen WF, Schoenle EJ, Froesch ER. Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A. Eur J Endocrinol 1994;131:251–7. ISSN 0804–4643 Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an iv bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 × 150 μg rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1–5) in the two patients were 9.6±1.3 and 9.2 ± 1.2 mmol/l, respectively, and fell to 4.4±0.4 and 5.1±0.5 mmol/l on treatment days 8–10. Fasting insulin (2950±450 and 690±125 pmol/l), C-peptide (2217±183 and 1317±235 pmol/l) and proinsulin control levels (125±35 and 66±0 pmol/l) also decreased by ~65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent. E Rudolf Froesch, Department of Internal Medicine, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland

scholarly journals Insulin-like Growth Factor I (IGF-I) Therapy in a Patient with Severe Insulin Resistance Syndrome

1994 ◽  
Vol 3 (Supple5) ◽  
pp. 239-239
Author(s):  
Yoshihiko Takahashi ◽  
Hiroko Kadowaki ◽  
Yasuo Akanuma ◽  
Takashi Kadowaki ◽  
Yoshio Yazaki
Keyword(s):  
Insulin Resistance ◽  
Growth Factor ◽  
Insulin Resistance Syndrome ◽  
Insulin Like Growth Factor ◽  
Severe Insulin Resistance ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

scholarly journals Long-term follow up in type A insulin resistant syndrome treated by insulin-like growth factor I.

1994 ◽  
Vol 71 (2) ◽  
pp. 144-146 ◽  
Author(s):  
H Ishihama ◽  
Y Suzuki ◽  
K Muramatsu ◽  
M Nagai ◽  
M Kokubo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Type A ◽  
Insulin Like Growth Factor ◽  
Insulin Resistant ◽  
Factor I ◽  
Long Term Follow Up ◽  
Growth Factor I

scholarly journals Oral administration of insulin-like growth factor-I from colostral whey reduces blood glucose in streptozotocin-induced diabetic mice

2011 ◽  
Vol 108 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Kyung-A Hwang ◽  
Yu-Jin Hwang ◽  
Woelkyu Ha ◽  
Young-Kug Choo ◽  
Kisung Ko
Keyword(s):  
Blood Glucose ◽  
Growth Factor ◽  
Oral Administration ◽  
Insulin Like Growth Factor ◽  
Diabetic Mice ◽  
Glucose Levels ◽  
Factor I ◽  
Blood Glucose Levels ◽  
Igf I ◽  
Growth Factor I

The aim of the present study was to investigate the effects of oral administration of the insulin-like growth factor-I-rich fraction (IGF-I-RF) from bovine colostral whey on the regulation of blood glucose levels in streptozotocin (STZ)-induced diabetic mice. We obtained a peptide fraction containing IGF-I (10 ng/mg protein) from Holstein colostrum within 24 h after parturition by using ultrafiltration. The blood glucose levels of STZ-induced diabetic mice fed with IGF-I-RF (50 μg/kg per d) were significantly reduced by 11 and 33 % at weeks 2 and 4, respectively (P < 0·05). The body weights of STZ-induced diabetic mice increased following the oral administration of the IGF-I-RF. The kidney weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of the IGF-I-RF, and the liver weights of STZ-induced diabetic mice decreased significantly (P < 0·05) following the administration of 50 μg/kg per d of the IGF-I-RF. The present results indicate that the IGF-I-RF obtained from Holstein colostrum could be a useful component for an alternative therapeutic modality for the treatment of diabetes in insulin-resistant patients.

Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency

1994 ◽  
Vol 131 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Maria C Thorén ◽  
Inga-Lena Wivall-Helleryd ◽  
Werner F Blum ◽  
Kerstin E Hall
Keyword(s):  
Growth Factor ◽  
Subcutaneous Administration ◽  
Metabolic Effects ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Igfbp 3

Thorén MC, Wivall-Helleryd I-L. Blum WF, Hall KE. Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency. Eur J Endocrinol 1994;131:33–40. ISSN 0804–4643 Insulin-like growth factor I (IGF-I) circulates bound to specific binding proteins (BPs) that modulate its effects at target cells. Hypoglycemia alters the serum levels of insulin-dependent IGFBPs and thus modifies the IGF-I action. We administered recombinant IGF-I (40 μg/kg body wt, from Kabi Pharmacia) in a morning dose (08.00 h) for seven consecutive days to six patients (21–47 years) with panhypopituitarism. This dose did not lead to hypoglycemia. Repeated blood sampling was performed on days 1 and 7, otherwise morning samples were drawn. The mean serum total IGF-I was maximal 3–4 h after the injection. A higher peak and basal value (p < 0.05) was observed on day 7 when compared to that observed on day 1. The concentrations were 237 vs 190 μg/l and 43 vs 22 μg/l. The mean free IGF-I increased concomitantly to 17 and 20 μg/l after 2–3 h on days 1 and 7. After 4 h, IGF-II was decreased (p <0.05) from 340 to 291 μg/l on day 1 and from 341 to 252 μg/l on day 7. The IGF-I area under the curve on days 1 and 7 was correlated to the IGFBP-3 levels. Only the patient with the highest IGFBP-3 level obtained IGF-I levels above 100 μg/l for 24 h. In spite of unchanged glucose levels, there was a modest suppression of insulin levels (p < 0.05) between 0 and 4 h from 102 to 78 pmol/l on day 1 and from 90 to 60 pmol/l on day 7 when the subjects were fasting. A small decline of mean potassium concentrations was found 2–6 h after the injection on day 1. During a week with daily injections, the morning serum IGF-I increased slightly in comparison to basal levels but no significant change in morning values of IGFBP-1, -2, -3, glucose and insulin were observed. Serum urea, creatinine, cholesterol and free fatty acid decreased significantly, indicating metabolic effects of IGF-I. Thus IGF-I has metabolic effects in doses not leading to hypoglycemia. To achieve a normal diurnal IGF-I level, recombinant IGF-I should be administered two or three times per 24 h in subjects with subnormal IGFBP-3 levels. Marja Thorén, Department of Endocrinology and Diabetology, Karolinska Hospital, S-171 76 Stockholm, Sweden

Diverse effects of insulin-like growth factor I on glucose, lipid, and amino acid metabolism

1992 ◽  
Vol 262 (1) ◽  
pp. E130-E133 ◽  
Author(s):  
S. D. Boulware ◽  
W. V. Tamborlane ◽  
L. S. Matthews ◽  
R. S. Sherwin
Keyword(s):  
Insulin Secretion ◽  
Amino Acid ◽  
Growth Factor ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Effects ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I) on glucose, amino acid, and free fatty acid (FFA) metabolism were examined in nine healthy nonobese subjects. Each received a 3-h primed continuous infusion of rhIGF-I (20 micrograms/kg bolus, 0.4 microgram.kg-1.min-1) while maintaining euglycemia using an exogenous glucose infusion. Total IGF-I levels increased from 125 +/- 11 to 444 +/- 22 ng/ml, and free IGF-I levels rose from undetectable to 73 +/- 5 ng/ml. Insulin levels fell from 95 +/- 9 to 64 +/- 8 pM, and C-peptide fell from 453 +/- 48 to 206 +/- 29 pM; circulating glucagon levels also declined from 72 +/- 9 to 42 +/- 4 pg/ml, rhIGF-I produced a two- to threefold increase in glucose uptake as measured by [3H] glucose (from 10.3 +/- 0.6 to 27.4 +/- 3 mumol.kg-1.m-1), and, despite the fall in insulin secretion, there was a marked 60-70% inhibition of hepatic glucose production. Furthermore, FFA and branched-chain amino acids declined by 40-60% (411 +/- 58 to 165 +/- 36 and 406 +/- 23 to 219 +/- 14 microM, respectively). Our data demonstrate that rhIGF-I has potent effects on glucose (hepatic and peripheral), lipid, and amino acid metabolism in normal humans. The scope of the actions of rhIGF-I closely resemble those of insulin, despite a concomitant inhibitory effect on insulin secretion.

scholarly journals Expression of insulin, insulin-like growth factor I and glucocorticoid receptor in rat uterus and embryo during decidualization, implantation and organogenesis

Reproduction ◽  
2003 ◽  
pp. 75-84 ◽  
Author(s):  
ET Korgun ◽  
G Dohr ◽  
G Desoye ◽  
R Demir ◽  
UA Kayisli ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucocorticoid Receptor ◽  
Receptor Expression ◽  
Metabolic Effects ◽  
Insulin Like Growth Factor ◽  
Mammalian Embryo ◽  
Endometrial Stromal Cells ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The significance of insulin, insulin-like growth factor I (IGF-I) and glucocorticoids to the early mammalian embryo is clear in that they are key regulators of both mitogenic and metabolic effects during development. In the present study, the temporal sequence of expression of the respective receptor proteins was investigated for the first time in the developing rat utero-embryonic unit between conception and day 12 of gestation using immunocytochemistry. Insulin, IGF-I and glucocorticoid receptor were expressed in embryonic tissues after the start of implantation, and were co-localized in the primary ectoderm, extraembryonic ectoderm as well as in the ectoplacental cone. The parietal endoderm was devoid of glucocorticoid receptor staining, whereas IGF-I receptor was absent in visceral endoderm. After completion of basic organogenesis, the neural tube, notochord, otic placode, Wolffian duct, mesonephros and intestinal tube expressed insulin, IGF-I and glucocorticoid receptor. The glucocorticoid receptor was not expressed in heart tube and dorsal aortae. Considerable amounts of insulin receptor were detected in trophoblast-derived giant cells. In the uterus, luminal epithelium, endometrial stromal and myometrial smooth muscle cells immunoreacted with antisera against insulin, IGF-I and glucocorticoid receptor. Endometrial glands remained negative for the glucocorticoid receptor throughout the gestational period investigated. Uterine hormone receptor expression reached a peak at days 4 and 5 of gestation in endometrial stromal cells and decidua, respectively. In conclusion, the demonstrated ontogenetic pattern of insulin, IGF-I and glucocorticoid receptor expression indicates the potential sites of biological action of the respective ligands, providing supportive evidence for their critical importance during the course of embryogenesis in rats.

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