scholarly journals Alterations in the Corneal Nerve and Stem/Progenitor Cells in Diabetes: Preventive Effects of Insulin-Like Growth Factor-1 Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hiroki Ueno ◽  
Takaaki Hattori ◽  
Yuta Kumagai ◽  
Noboru Suzuki ◽  
Satoki Ueno ◽  
...  
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Diabetic Group ◽  
Insulin Like Growth Factor ◽  
Diabetic Mice ◽  
Cell Markers ◽  
Igf I ◽  
Corneal Nerve

This study aimed to investigate whether corneal nerve and corneal stem/progenitor cells are altered in insulin-like growth factor-I (IGF-I-) treated individuals with diabetes. A group consisting of db/db mice with type 2 diabetes mellitus (DM) and a wild-type group were assessed by neural and corneal stem/progenitor cell markers immunostaining and real-time PCR. Moreover, the expression of corneal nerve and stem/progenitor cell markers was examined in IGF-1-treated diabetic mice. Compared with a normal cornea, swelling and stratification of the corneal epithelium were noted in db/db mice. Beta-III tubulin immunostaining revealed that the corneal subbasal plexuses in diabetic mice were thinner with fewer branches. mRNA expression levels ofHes1,Keratin15, andp75(corneal stem/progenitor cell markers) and the intensity and number of positive cells of Hes1 and Keratin19 immunostaining diminished in the diabetic corneas. Compared with the subbasal nerve density in the normal group, a decrease in the diabetic group was observed, whereas the corneal subbasal nerve density increased in IGF-1-treated diabetic group. The decreased expression of Hes1 and Keratin19 was prevented in IGF-1-treated diabetic group. Our data suggest that corneal nerve and stem/progenitor cells are altered in type 2 DM, and IGF-I treatment is capable of protecting against corneal damage in diabetes.

scholarly journals Insulin-like growth factor I, binding proteins -1 and -3, risk of type 2 diabetes and macronutrient intakes in men

2019 ◽  
Vol 121 (8) ◽  
pp. 938-944
Author(s):  
Minna E. Similä ◽  
Jukka P. Kontto ◽  
Jarmo Virtamo ◽  
Katja A. Hätönen ◽  
Liisa M. Valsta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Binding Proteins ◽  
Conditional Logistic Regression ◽  
Intervention Group ◽  
Diabetes Risk ◽  
Insulin Like Growth Factor ◽  
Baseline Serum ◽  
Igf I

AbstractThe insulin-like growth factor (IGF) axis may be involved in the development of type 2 diabetes. We examined the associations of IGF-I and IGF binding proteins (IGFBP)-1 and -3 with diabetes risk and evaluated macronutrient intakes related to the observed associations. In a nested case–control study of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers aged 50–69 years, the IGF variables were measured from baseline serum samples for a random sample of 310 men with diabetes diagnosed during a 12-year follow-up and for 310 controls matched by age, recruitment day and intervention group. Diet at baseline was assessed using a validated FFQ. The associations of IGF proteins with diabetes risk were estimated using conditional logistic regression and the associations with macronutrient intakes using linear regression. IGF-I and IGFBP-3 were not associated with the incidence of diabetes. Higher IGFBP-1 was associated with lower diabetes risk in an unadjusted crude model (OR 0·25; 95 % CI 0·15, 0·42 in the highest quartile compared with the lowest), but not after adjustment for BMI (corresponding OR 0·76; 95 % CI 0·41, 1·40). Intakes of carbohydrates, plant protein and milk protein associated positively and intake of meat protein and fat negatively with IGFBP-1 (P<0·005). IGFBP-1 was inversely associated with diabetes risk, but the association was substantially dependent on BMI. The associations between macronutrient intakes and IGFBP-1 may reflect influences of nutrients or foods on insulin concentrations.

scholarly journals Structural Analogs of Human Insulin-like Growth Factor (IGF) I with Altered Affinity for Type 2 IGF Receptors

1989 ◽  
Vol 264 (4) ◽  
pp. 2199-2202
Author(s):  
M A Cascieri ◽  
G G Chicchi ◽  
J Applebaum ◽  
B G Green ◽  
N S Hayes ◽  
...  
Keyword(s):  
Growth Factor ◽  
Human Insulin ◽  
Insulin Like Growth Factor ◽  
Igf Receptors ◽  
Igf I

scholarly journals Kidney Growth in Normal and Diabetic Mice is not Affected by Human Insulin-Like Growth Factor Binding Protein-1 Administration

2005 ◽  
Vol 230 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Vesna Cingel-Ristic ◽  
Bieke F. Schrijvers ◽  
Arlène K. van Vliet ◽  
Ruth Rasch ◽  
Victor K. M. Han ◽  
...  
Keyword(s):  
Growth Factor ◽  
Messenger Rna ◽  
Binding Protein ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Diabetic Mice ◽  
Kidney Weight ◽  
Local Synthesis ◽  
Igf I ◽  
Renal Changes

Insulin-like growth factor I (IGF-I) accumulates in the kidney following the onset of diabetes, initiating diabetic renal hypertrophy. Increased renal IGF-I protein content, which is not reflected in messenger RNA (mRNA) levels, suggests that renal IGF-I accumulation is due to sequestration of circulating IGF-I rather than to local synthesis. It has been suggested that IGF-I is trapped in the kidney by IGF binding protein 1 (IGFBP-1). We administered purified human IGFBP-1 (hIGFBP-1) to nondiabetic and diabetic mice as three daily sc injections for 14 days, starting 6 days after induction of streptozotocin diabetes when the animals were overtly diabetic. Markers of early diabetic renal changes (i.e., increased kidney weight, glomerular volume, and albuminuria) coincided with accumulation of renal cortical IGF-I despite decreased mRNA levels in 20-day diabetic mice. Human IGFBP-1 administration had no effect on increased kidney weight or albuminuria in early diabetes, although it abolished renal cortical IGF-I accumulation and glomerular hypertrophy in diabetic mice. Increased IGF-I levels in kidneys of normal mice receiving hIGFBP-1 were not reflected on kidney parameters. IGFBP-1 administration in diabetic mice had only minor effects on diabetic renal changes. Accordingly, these results did not support the hypothesis that IGFBP-1 plays a major role in early renal changes in diabetes.

scholarly journals Insulin-Like Growth Factor Binding Protein-1 Is Elevated in Patients With Polycythemia Vera and Stimulates Erythroid Burst Formation In Vitro

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 1862-1869 ◽  
Author(s):  
Amer M. Mirza ◽  
Shereen Ezzat ◽  
Arthur A. Axelrad
Keyword(s):  
Growth Factor ◽  
Polycythemia Vera ◽  
Progenitor Cells ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Igf I ◽  
Increased Sensitivity ◽  
Igfbp 3

Abstract Previously, we found that, in the myeloproliferative disorder polycythemia vera (PV), circulating erythroid progenitor cells were hypersensitive to insulin-like growth factor I (IGF-I), an effect shown to occur through the IGF-I receptor. Also, in cells of PV patients, the IGF-I receptor was hyperphosphorylated on tyrosine residues under basal conditions, and its tyrosine phosphorylation in response to exogenous IGF-I was strongly augmented. Thus, because IGF-I appeared to play a role in the pathogenesis of PV, we wished to assess its level in the circulation of these patients. Normally, most of the circulating IGF-I is bound to specific high-affinity IGF binding proteins that can regulate its activity. We determined the circulating levels of IGF-I and two of its key binding proteins, IGFBP-1 and IGFBP-3. In two separate experiments, plasma samples from a total of 23 PV patients age- and sex-matched with 41 normal individuals were compared by radioimmunoassay. The levels of IGFBP-1 in patients with PV (37.80 ± 4.33 μg/L) were more than fourfold higher than in normals (9.34 ± 1.34 μg/L) or patients with secondary erythrocytosis (9.47 ± 1.96 μg/L), whereas the plasma concentrations of IGFBP-3 and IGF-I in these patients were similar to those of normal subjects. Because circulating IGFBP-1 levels may be influenced by insulin, we measured the concentrations of insulin in the same samples. Our data showed that the elevation of circulating IGFBP-1 in PV could not be attributed to low levels of insulin in these patients. The substantial increase in concentration of IGFBP-1 was confirmed on ligand blots performed with 125I–IGF-I. IGFBP-1 can be either inhibitory or stimulatory to the action of IGF-I under different conditions. We reasoned that if IGFBP-1 were stimulatory for erythropoiesis, an elevated IGFBP-1 level could help to explain the increased sensitivity to IGF-I observed in PV. If IGFBP-1 were inhibitory, it might suggest a compensatory mechanism in which a hyperphosphorylated IGF-I receptor in PV might induce a negative modulator of IGF-I action, in this case IGFBP-1. To distinguish between these two hypotheses, we titrated the effect of IGFBP-1 in the presence of IGF-I with respect to erythroid burst formation and found that IGFBP-1 was strikingly stimulatory. The elevated level of IGFBP-1 coupled with its ability to stimulate erythroid burst formation provide an attractive mechanism to account for the increased sensitivity of erythroid progenitor cells to IGF-I and the consequent overproduction of red blood cells characteristic of PV.

Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism

2006 ◽  
Vol 291 (4) ◽  
pp. R880-R884 ◽  
Author(s):  
Meijing Wang ◽  
Paul R. Crisostomo ◽  
Christine Herring ◽  
Kirstan K. Meldrum ◽  
Daniel R. Meldrum
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Progenitor Cells ◽  
P38 Mapk ◽  
Progenitor Cell ◽  
Tissue Loss ◽  
Igf I ◽  
P38 Mapk Inhibitor ◽  
Mapk Inhibitor ◽  
Dependent Mechanism

Accumulating evidence suggests that progenitor cells may decrease destructive inflammation and reduce tissue loss by antiapoptotic mechanisms. However, they remain poorly characterized, and many questions remain regarding the mechanisms by which they may positively affect wound healing, tissue remodeling, or tissue regeneration. It has been speculated that various growth factors are responsible, but what components of the wound milieu stimulate progenitor cell production of growth factors and by what mechanisms? We hypothesized that tumor necrosis factor-α (TNF-α) stimulated progenitor cell secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor I (IGF-I) by a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism. Human mesenchymal stem cells (hMSCs) and human adipose progenitor cells (hAPCs) were divided into four groups: control, p38 MAPK inhibitor (p38MKI), TNF, and TNF + p38MKI. After 24 h of incubation, supernatants were harvested for ELISA of VEGF, HGF, and IGF-I. Cells were collected for Western blot analysis of p38 MAPK activation. Secretion of VEGF, HGF, and IGF-I in hMSCs and hAPCs was significantly increased by stimulation with TNF and was associated with increased activation of p38 MAPK. The p38 MAPK inhibitor decreased production of TNF-stimulated VEGF, HGF, and IGF-I in hMSCs and hAPCs. However, p38 MAPK inhibitor alone had no effect on production of growth factors. These data demonstrate that progenitor cells are potent sources of VEGF, HGF, and IGF-I. TNF, a prominent tissue cytokine, strongly stimulated production of growth factors by hMSCs and hAPCs via a p38 MAPK-dependent mechanism.

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.

Receptors for insulin-like growth factor-II in the growing tip of the deer antler

1993 ◽  
Vol 138 (2) ◽  
pp. 233-NP ◽  
Author(s):  
J. L. Elliott ◽  
J. M. Oldham ◽  
G. R. Ambler ◽  
P. C. Molan ◽  
G. S. G. Spencer ◽  
...  
Keyword(s):  
Growth Factor ◽  
Specific Binding ◽  
Cross Linking ◽  
Insulin Like Growth Factor ◽  
Deer Antler ◽  
Reducing Conditions ◽  
Factor Ii ◽  
Igf I ◽  
Igf Receptor

ABSTRACT Insulin-like growth factor-II (IGF-II) binding in the growing tip of the deer antler was examined using autoradiographical studies, radioreceptor assays and affinity cross-linking studies. Antler tips from red deer stags were removed 60 days after the commencement of growth, and cryogenically cut into sections. Sections were incubated with radiolabelled IGF-II, with or without an excess of competing unlabelled IGF-II and analysed autoradiographically. Radiolabelled IGF-II showed high specific binding in the reserve mesenchyme and perichondrium zones, which are tissues undergoing rapid differentiation and cell division in the antler. Binding to all other structural zones was low and significantly (P<0·001) less than binding to the reserve mesenchyme/perichondrium zones. Radioreceptor assays on antler microsomal membrane preparations revealed that the IGF-II binding was to a relatively homogeneous receptor population (Kd= 1·3 × 10−10 mol/l) with characteristics that were not entirely consistent with those normally attributed to the type 2 IGF receptor. Tracer binding was partly displaceable by IGF-I and insulin at concentrations above 10 nmol/l. However, affinity cross-linking studies revealed a single band migrating at 220 kDa under non-reducing conditions, indicative of the type 2 IGF receptor. These results indicate that, in antler tip tissues, IGF-II binds to sites which have different binding patterns and properties from receptors binding IGF-I. This may have functional significance as it appears that, whilst IGF-I has a role in matrix development of cartilage, IGF-II may have a role in the most rapidly differentiating and proliferating tissues of the antler. Journal of Endocrinology (1993) 138, 233–241

scholarly journals Renal hypertrophy in hyperglycemic non-obese diabetic mice is associated with persistent renal accumulation of insulin-like growth factor I.

1997 ◽  
Vol 8 (3) ◽  
pp. 436-444 ◽  
Author(s):  
Y Segev ◽  
D Landau ◽  
M Marbach ◽  
N Shehadeh ◽  
A Flyvbjerg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Therapy ◽  
Type I ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Diabetic Mice ◽  
Renal Hypertrophy ◽  
Kidney Weight ◽  
Igf System ◽  
Igf I

The non-obese diabetic mouse is a model of spontaneous insulin-dependent diabetes as a result of autoimmune destruction of pancreatic beta cells, similar to the disease seen in human Type I diabetes. This mouse strain develops glomerular lesions reminiscent of those seen in human disease. The study presented here investigated the changes in renal insulin-like growth factor (IGF) system in hyperglycemic non-obese diabetic mice. Female non-obese diabetic mice and their age- and sex-matched controls were euthanized 4 days, 2 wk, and 4 wk after the onset of glycosuria. Kidney weight increased in diabetic mice, beginning at 2 wk after the onset of glycosuria. This renal hypertrophy was associated with an increase in renal extractable IGF-I protein. However, a decrease in IGF-I mRNA was observed at the same time. Serum IGF-I levels remained stable after 2 wk of diabetes and decreased at 1 month. No change was detected in renal IGF-I receptor mRNA levels. Renal cortical IGF binding protein (IGFBP)-1 mRNA levels were increased. Ligand blot analysis revealed a significant increase in serum and renal 30-kd IGFBP and a decrease in serum and kidney IGFBP-3 and IGFBP-4 at 30 days of diabetes. Insulin therapy prevented the increases in kidney weight, renal IGF-I, and 30-kd IGFBP, but did not reverse the decreased serum IGF-I levels observed at 1 month of diabetes. In summary, renal hypertrophy in non-obese diabetic mice is associated with a persistent accumulation of renal IGF-I and, IGFBP-1. These changes were partially reversed with insulin therapy, which did not correct the hyperglycemia, suggesting an important role for insulin deficiency in mediating these changes in the IGF system. These findings suggest that the IGF system may play a potential role in the development of diabetic nephropathy.

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