scholarly journals Effect of diabetes mellitus on levels of insulin-like growth factors and their carrier proteins in Guerin’s carcinoma and it’s perifocal tissue in rats

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.

Author(s):  
I.A. Goroshinskaya ◽  
E.M. Frantsiyants ◽  
I.V. Kaplieva ◽  
L.A. Nemashkalova ◽  
L.K. Trepitaki ◽  
...  

Taking into account cancer and diabetes comorbidity, the role of free radicals in these conditions and the dependence of pathological processes on the gender of animals, the aim of the study was to examine lipid peroxidation (LPO) intensity and the activity of the key antioxidant enzyme superoxide dismutase (SOD) in the heart, kidneys, liver, and in tumors of male and female rats with diabetes mellitus (DM), Guerin's carcinoma (GC) or both diseases. Materials and Methods. The study included 80 white nonlinear male and female rats (180–220 g). The animals were divided into 4 groups, each group included 10 animals (either male or female). At the time of GC inoculation, the blood glucose level in animals with alloxan diabetes was 25.4±1.2 mmol/L. The authors used conventional spectrophotometric methods to examine the content of malondialdehyde (MDA), diene conjugates (DC), and SOD activity. Statistical analysis was performed using Statistical analysis software Statistica 10.0. Results. The most pronounced changes in the studied parameters were found in the heart of female rats with isolated GC and associated diabetes mellitus: more than a threefold increase in MDA, a significant increase in DC against the background of an increase in SOD activity (by 5.5–6.3 times in comparison to intact animals). The amount of MDA in GC tissue depended on the tumor size: the maximum increase in both parameters was observed in male rats with GC growth and associated DM. Conclusion. The changes in the content of LPO products and SOD activity in the heart, kidneys, and liver of rats with diabetes mellitus and tumor growth depend on the type of the examined tissue and the gender of the animals. Disorders of the redox status found in the heart tissue can make a significant contribution to cardiopathology, which is often observed in diabetes mellitus and malignant tumor growth. Key words: diabetes mellitus, Guerin's carcinoma, rats, combined pathology, heart, kidneys, liver, malondialdehyde, diene conjugates, superoxide dismutase. Учитывая коморбидность рака и диабета, роль свободнорадикальных процессов при этих состояниях и зависимость течения патологических процессов от пола животных, целью исследования явилось изучение интенсивности перекисного окисления липидов (ПОЛ) и активности ключевого антиоксидантного фермента супероксиддисмутазы (СОД) в сердце, почках, печени, а также в опухоли крыс разного пола при сахарном диабете (СД), карциноме Герена (КГ) и при их сочетании. Материалы и методы. В исследование были включены 80 белых нелинейных крыс обоего пола массой 180–220 г, разделенных на 4 группы по 10 животных каждого пола. На момент перевивки КГ уровень глюкозы в крови животных с аллоксановым СД составил 25,4±1,2 ммоль/л. Содержание малонового диальдегида (МДА), диеновых конъюгатов (ДК) и активность СОД исследованы общепринятыми спектрофотометрическими методами. Статистический анализ проведен с использованием программы Statistica 10.0. Результаты. Наиболее выраженные изменения изученных показателей выявлены в сердце самок при изолированной КГ и КГ, растущей на фоне СД: более чем трехкратное увеличение МДА, значимый прирост ДК на фоне повышения активности СОД в 5,5–6,3 раза относительно интактных животных. В ткани КГ прослеживалась зависимость степени выраженности увеличения содержания МДА от размеров опухоли: максимальное увеличение обоих показателей наблюдалось у самцов при росте КГ на фоне СД. Выводы. Направленность изменения содержания продуктов ПОЛ и активности СОД в сердце, почках и печени крыс при СД и опухолевом росте зависит от типа исследованной ткани и пола животных. Обнаруженные в ткани сердца нарушения редокс-статуса могут вносить значимый вклад в развитие кардиопатологии, часто наблюдаемой при СД и злокачественном росте. Ключевые слова: сахарный диабет, карцинома Герена, крысы, сочетанная патология, сердце, почки, печень, малоновый диальдегид, диеновые конъюгаты, супероксиддисмутаза.


1999 ◽  
Vol 54 (3) ◽  
pp. B111-B115 ◽  
Author(s):  
S. Severgnini ◽  
D. T. Lowenthal ◽  
W. J. Millard ◽  
F. A. Simmen ◽  
B. H. Pollock ◽  
...  

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.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fawzi Babiker ◽  
Aishah Al-Jarallah ◽  
Mariam Al-Awadi

Background. Aging, left ventricular hypertrophy (LVH), diabetes mellitus, and pregnancy are well-recognized risk factors that increase the prevalence of cardio-ischemic events and are linked to poor clinical recovery following acute myocardial infarction. The coexistence of these risk factors with ischemic heart disease (IHD) deteriorates disease prognosis and could potentially lead to fatal arrhythmias and heart failure. The objective of this study was to investigate the vulnerability of hearts with aging, LVH, diabetes, and pregnancy to ischemic insult and their response to pacing postconditioning- (PPC-) induced heart protection. Methods. Hearts isolated from aged, spontaneously hypertensive and diabetic male and female rats and hearts from pregnant female rats (n=8 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Hemodynamics data were computed digitally, and cardiac damage was accessed by measurements of infarct size and cardiac enzyme release. Results. There were no significant differences in the vulnerability of all hearts to ischemic insult compared to their respective controls. PPC improved cardiac hemodynamics and reduced infarct size and cardiac enzyme release in hearts isolated from aged and spontaneously hypertensive female rats and female rats with hypertrophied hearts subjected to PPC (P<0.001). Aged or hypertrophied male hearts were not protected by PPC maneuver. Moreover, the protective effects of PPC were lost in diabetic male and female hearts although retained in hearts from pregnant rats. Conclusions. We demonstrate that aging, LVH, diabetes mellitus, and pregnancy do not affect cardiac vulnerability to ischemic insult. Moreover, PPC mediates cardioprotection in a gender-specific manner in aged and spontaneously hypertensive rats. Diabetes mellitus provokes the protective effects of PPC on both genders equally. Finally, we demonstrate that PPC is a new cardioprotective maneuver in hearts from pregnant female rats.


1961 ◽  
Vol 38 (1) ◽  
pp. 50-58 ◽  
Author(s):  
N. E. Borglin ◽  
L. Bjersing

ABSTRACT Oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) is a weakly oestrogenic substance which, however, in contrast to what was formerly believed, is of physiological significance. Its effect is localized largely to the uterine cervix and vagina. Clinical experience argues both for and against an effect on the pituitary gland. This investigation is concerned with the morphological changes in the pituitary gland and adrenal cortex of gonadectomized male and female rats after the injection of oestriol. It was found that oestriol has the same type of action on these glands as other oestrogens, but under the experimental conditions used, this effect proved much weaker than that produced by oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


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