Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes

2009 ◽  
Vol 106 (01) ◽  
pp. 79-84 ◽  
Author(s):  
A. Hübler ◽  
K. Abendroth ◽  
T. Keiner ◽  
W. Stöcker ◽  
E. Kauf ◽  
...  
2013 ◽  
Vol 2013 ◽  
pp. 1-37 ◽  
Author(s):  
Rosalyne L. Westley ◽  
Felicity E. B. May

Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.


2021 ◽  
Vol 67 (5) ◽  
pp. 34-42
Author(s):  
E. M. Frantsiyants ◽  
E. I. Surikova ◽  
I. V. Kaplieva ◽  
V. A. Bandovkina ◽  
I. V. Neskubina ◽  
...  

Diabetes mellitus and malignant tumors are among the most common and complex diseases. Epidemiological studies have shown a strong relationship between these pathologies. The causality of this relationship has not yet been unambiguously established, but a number of probable biological mechanisms have been proposed to explain it through the effects of hyperglycemia, hyperinsulinemia on the process of oncogenesis. An important role in this is played by the axis of insulin-like growth factors, their receptors and binding proteins (IGF / IGFR / IGFBP). The review provides data on the structural elements of the insulin / IGF / IGFR / IGFBP signaling axis and their internal relationships in diabetes mellitus and in the development of malignant tumors. Significant changes in the axis that occur during the formation of the diabetic environment prepare the background, which, under certain conditions, can lead to the stimulation or inhibition of tumor development. The considered signaling system, playing a significant role in the physiology of normal cells, often functions as a decisive factor in the survival of tumor cells, providing fine context-dependent regulation of many cellular processes associated with oncogenesis. However, despite many years of in-depth studies of the pathogenesis of diabetes mellitus and malignant tumors, the molecular mechanisms of the relationship between these pathologies are still largely unclear, and the internal heterogeneity of pathologies complicates research and interpretation of the results, leaving many questions.


Diabetes ◽  
1984 ◽  
Vol 33 (8) ◽  
pp. 790-793 ◽  
Author(s):  
T. J. Merimee ◽  
D. F. Gardner ◽  
J. Zapf ◽  
E. R. Froesch

2009 ◽  
Vol 28 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Milena Weber ◽  
Ivona Baričević-Jones ◽  
Romana Masnikosa ◽  
Dejan Filimonović ◽  
Željko Miković ◽  
...  

Receptors and Binding Proteins for Insulin and Insulin-Like Growth Factors in the Placenta of Healthy Mothers and Mothers with Insulin-Dependent Diabetes Mellitus The IGF system of human placenta consists of insulin-like growth factors (IGF)-I and -II, their receptors (IGF-1R and IGF-2R), and binding proteins (IGFBP-1 to -6). Due to many structural and metabolic similarities with insulin, the IGF system cannot be examined separately from insulin and its receptor (IR). In this study gel filtration was used to detect solubilized membrane proteins of the placenta obtained from healthy mothers and mothers with IDDM. In order to detect placental membrane proteins that bind IGF molecules (and insulin), the solubilized membranes were incubated with each of the three 125I-labelled ligands: 125I-IGF-I, 125I-IGF-II and 125I-insulin prior to gel filtration chromatography. The biochemical evidence of the presence of receptors for insulin and IGFs, as well as that of IGFBP-1 were obtained by immunoblotting. Herein we demonstrated that, considering IGF and insulin receptor content, the placental tissue obtained from mothers with IDDM was not different from that obtained from healthy mothers. However, the concentration of IGFBP-1 differed between the examined placentas. IDDM in mothers caused an increase in the amount of IGFBP-1 in their placentas and, consequently, the amount of the labelled ligand bound to it. The redistribution of IGFs between the receptors and IGFBP-1 may be involved in regulatory mechanisms in the placenta of mothers with IDDM.


2021 ◽  
Vol 8 (4) ◽  
pp. 44-52
Author(s):  
E. M. Frantsiyants ◽  
V. A. Bandovkina ◽  
I. V. Kaplieva ◽  
E. I. Surikova ◽  
I. V. Neskubina ◽  
...  

Purpose of the study. Diabetes mellitus (DM) is considered an independent risk factor for higher cancer incidence and death rates. The system of insulin-like growth factors and their carrier proteins (IGF and IGFBP) and hyperglycemia create favorable conditions for the proliferation and metastasis of cancer cells.Materials and methods. Outbred male and female rats were divided into groups (n = 8 each): controls - with Guerin's carcinoma; main group - Guerin's carcinoma growing in presence of DM. Experimental DM was reproduces in animals by the single intraperitoneal alloxan injection (150 mg/kg body weight). After 10 days of the carcinoma growth, levels of IGF and IGFBP in the tumor and in it's perifocal area were measured using ELISA.Results. DM in females upregulated levels of glucose both in the tumor and in perifocal tissues by 1.8 (p < 0.05) and 8.1 times, respectively, but caused opposite changes in IGF-I - it's increase by 6.3 times in the tumor and decrease by 3.2 times in the perifocal area; as a result, such tumors with small primary nodes were more "aggressive" and actively metastasized. In males, induced DM downregulated levels of glucose, IGF-II and IGFBP2 in the carcinoma by 8.4, 3.1 and 1.7 (p < 0.05) times, respectively, and increased levels of IGF-I and IGFBP2 by 1.4 and 1.3 times (p < 0.05) in the perifocal area without changing glucose levels; as a result, tumor volumes exceeded the values in the standard growth, without metastasizing into visceral organs.Conclusion. We revealed gender differences in changing levels of glucose and IGF both in the tumor and in it's perifocal tissue in rats with Guerin's carcinoma growing in presence of DM; these differences could determine different tumor growth dynamics in male and female rats.


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