Insulin Homeostasis
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2021 ◽  
Ou Wang ◽  
Li Han ◽  
Haishuang Lin ◽  
Mingmei Tian ◽  
Shuyang Zhang ◽  

A large population of people is affected by obesity (OB) and its associated type 2 diabetes mellitus(T2DM). There are currently no safe and long-lasting anti-OB/T2DM therapies. Clinical data and preclinical transplantation studies show that transplanting metabolically active brown adipose tissue (BAT) is a promising approach to prevent and treat OB and its associated metabolic and cardiovascular diseases. However, most transplantation studies used mouse BAT, and it is uncertain whether the therapeutic effect would be applied to human BAT since human and mouse BATs have distinct differences. Here, we report the fabrication of three-dimensional (3D) human brown adipose microtissues, their survival and safety, and their capability to improve glucose and insulin homeostasis and manage body weight gain in high-fat diet (HFD)-induced OB and diabetic mice.

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Ahmed Mohamed Nour El-Din Hashaad ◽  
Reda Mokhtar Kamal Ghanem ◽  
Sara Abouelfath Abouelasrar Gad Dawoud

Abstract Background Polycystic ovary syndrome (PCOS) is considered one of the most common endocrine disorders affecting females in their reproductive age. In PCOS, an imbalance between androgens, anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH), cause a halt of follicular growth. Insulin resistance (IR) is another important component of PCOS. There is increasing evidence that vitamin D affects insulin and glucose metabolism, Vitamin D plays a vital role in the regulation of glucose-insulin homeostasis. Objectives to assess the efficacy of vitamin D supplementation in improving ovulation induction in PCOS women (1ry outcome) and increasing pregnancy rate (secondary outcome). Patients and Methods 120 women diagnosed PCOS according to Rotterdam criteria and were resistant to CC treatment were randomly allocated into equal two groups: Group V: number of 60 patients received cholecalciferol + Metformin for 2 months. Group C: 60 patients received Metformin 2 months. After two months from the start:Both study groups started induction with Clomiphene Citrate added every month starting from the 3rd month to the 5th month (3 cycles of ovulation induction) in addition to previous drugs mentioned. Results In our study results, regulation of menstrual cycle occured in 63.6% of women who recieved vitamin D + metformin (group V) and ovulation was confirmed in 34.5% of the total number (55 women). Later, 18% of them got pregnant after 3 months of treatment. Added to that 16 women out of 39 (41%) got pregnant by the end of the follow up period with cumulative pregnancy rate (53%). On the other hand menstrual regularity in (group C: metformin) recorded 61% with ovulation percentage of 26.9% (n = 54). Followed by 14.8% pregnancy rate at the 3rd month., which increased to 27.5% by the end of the study out of 47.5% ovulated women (n = 40). Cumulative pregnancy rate 40%. Conclusion From the current study we can conclude that there is no significant difference of adding vitamin D to CC resistant PCOS regarding ovulation and pregnancy rates. However, it can augment metformin action and improves its outcome.

Basma S. Ismail ◽  
Eman S. Abdel-Reheim ◽  
Hanan A. Soliman ◽  
Basant Mahmoud

Liver is considered as significant organ within body. Aims: Our survey aimed in illustrating protective effectiveness of gallic acid (GA) against high fat regimen nonalcoholic fatty liver disease (NAFLD). Study design: In our study, Rats were classified into 3 groups; control, orally given fatty-sucrosed diet, gallic acid treated groups. Methodology: They were evaluated through measuring hepatic cholesterol and triglyceride, alanine and aspartate aminotransferases and gammaglutamyl-transferase; total, direct and indirect bilirubin; total protein, albumin and globulin; hepatic and adipose malondialdehyde, glutathione-S-transferase, superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase activities; glucose, insulin, homeostasis model assessment of insulin resistance, leptin and adiponectin; tumor necrosis factor alpha, interleukin-17 and interleukin-1beta; fatty acid synthase, acetyl-Coenzyme A carboxylase-α  and HMGCoA reductase. Results: Our results demonstrated that GA ameliorated the elevated lipid, serum liver function enzymes, bilirubin and the decreased L.glycogen levels and serum protein profile. GA improved the hepatic and adipose antioxidants activities by decreasing MDA and increasing GST, SOD, Cat, GSH and GPx activities. GA ameliorated the elevated Glu, INS, HOMA-IR, LEP and the decreased adiponectin levels. Moreover, GA ameliorated the elevated TNF-α, IL-17, IL-1β, FAS, ACC-α and HMGCR levels. Liver and adipose histopathologies confirmed our results. Conclusion: Gallic acid intake exhibited a beneficial therapeutic effect on nonalcoholic fatty liver disease rats as anti-inflammatory and antioxidant agent.

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2263
Agata Barzowska ◽  
Barbara Pucelik ◽  
Katarzyna Pustelny ◽  
Alex Matsuda ◽  
Alicja Martyniak ◽  

The rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and a durable cure has not yet been achieved. We demonstrate that our set of small molecule inhibitors of DYRK1A kinase potently promotes β-cell proliferation, enhances long-term insulin secretion, and balances glucagon level in the organoid model of the human islets. Comparable activity is seen in INS-1E and MIN6 cells, in isolated mice islets, and human iPSC-derived β-cells. Our compounds exert a significantly more pronounced effect compared to harmine, the best-documented molecule enhancing β-cell proliferation. Using a body-like environment of the organoid, we provide a proof-of-concept that small–molecule–induced human β-cell proliferation via DYRK1A inhibition is achievable, which lends a considerable promise for regenerative medicine in T1DM and T2DM treatment.

2021 ◽  
Vol 21 (1) ◽  
Yang Xiao ◽  
Jingjing Mao ◽  
Xiaodong Mao ◽  
Qifeng Wang ◽  
Xingjia Li ◽  

Abstract Objective To explore the association between metabolic syndrome (MetS) and its component and thyroid volume in Chinese adolescents, and to compare the detection rate of MetS under the three different diagnostic criteria. Methods A total of 1097 school students (610 males and 487 females, ages 12–15 years) were enrolled. All the participants underwent physical examination, biochemical test, and thyroid gland ultrasonography. The thyroid volume of normal, overweight and obese group was compared. We also analyzed the association between the number of MetS components and thyroid volume. Linear and multiple linear regression were applied to explore the association between metabolic parameters and thyroid volume. Results The thyroid volume of the males in overweight (t = 3.784, P < 0.001) and obese group (t = 5.068, P < 0.001) was significantly larger than that in normal group; the thyroid volume of the females in overweight group (t = 4.627,P < 0.001) was significantly larger than that of normal group. As the number of MetS components increased, the thyroid volume also increased significantly (F = 10.64, P < 0.01). Height, weight, body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and triglyceride were all positively associated with thyroid volume in the adolescents (P all < 0.001). Meanwhile, there was a negative association between high-density lipoprotein cholesterol (HDL-C) and thyroid volume (P < 0.001). According to multiple linear regression, waist circumference (β = 0.029, 95 %CI: 0.015 ~ 0.042; P < 0.01) and waist height ratio (β = 3.317, 95 %CI: 1.661 ~ 4.973; P < 0.01) were predict factors of thyroid volume. No statistical difference was found in the detection rates of metabolic syndrome under the three diagnostic criteria. Conclusions Overweight, obesity and metabolic syndrome was associated with adolescent thyroid volume. Central obesity may be an independent risk factor for thyroid enlargement in adolescents.

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Daniel de Luis ◽  
Olatz Izaola ◽  
David Primo

Background and Aims. This APOA5-1131C allele is related with a higher serum triglyceride levels and perhaps a different metabolic response to a dietary intervention. The aim of the present investigation was to evaluate SNP rs662799 in the APOA5 gene and its associations with metabolic effects after a hypocaloric diet with Mediterranean pattern. Methods. A population of 363 Caucasian obese patients was enrolled. Anthropometric parameters and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, adiponectin, resistin, and leptin levels) were measured, at basal time and after 3 months. All patients were genotyped in the rs662799 polymorphism. Results. The APOA5 variant distribution was as follows: 89.3% ( n = 324 ) (TT) were homozygous for the T allele, 10.5% ( n = 38 ) (TC) were heterozygous, and 0.2% ( n = 1 ) (CC) were homozygous for the C allele. Triglyceride levels were higher in patients with the C allele. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, adiponectin, leptin, and adiponectin/leptin ratio improved significantly in both genotype groups TT and TC+CC. After dietary intervention, insulin levels (delta: − 3.6 ± 0.8   UI / L vs. − 1.5 ± 0.6   UI / L ; P = 0.03 ), HOMA-IR (delta: − 1.5 ± 0.4   units vs. − 0.3 ± 0.2   units ; P = 0.02 ), and triglyceride levels (delta: − 19.3 ± 4.2   mg / dL vs. − 3.2 ± 3.1   mg / dL ; P = 0.02 ) decreased in non-C allele carriers. Conclusions. C allele carriers of rs662799 of the APOA5 gene did not show an improvement in triglyceride, insulin, and HOMA-IR levels after a significant weight loss due to a hypocaloric diet with a Mediterranean pattern.

Małgorzata Jamka ◽  
Anna Morawska ◽  
Patrycja Krzyżanowska-Jankowska ◽  
Joanna Bajerska ◽  
Juliusz Przysławski ◽  

It is well known that rapeseed oil improves lipid profile and has antiatherosclerotic properties. Recently, amaranth oil has also become popular due to its potential health benefits. However, the effect of this oil on atherosclerosis markers in humans is not clear. Therefore, this study aimed to compare the effect of amaranth and rapeseed oils on selected atherosclerosis-related parameters in overweight and obese subjects. In this randomized cross-over study, 44 subjects were instructed to consume 20 mL of amaranth oil and rapeseed oil during two consecutive three-week intervention periods separated by a washout period of the same duration as the intervention. The outcome variables included changes in tumor necrosis factor-alpha, adiponectin, oxidized low-density lipoprotein, apolipoproteins (Apo) A1, B and E as well as glucose and insulin homeostasis markers. Compared to rapeseed oil, amaranth oil had a slight positive effect on adiponectin levels (mean (95% confidence interval): 0.55 (0.22–0.89) vs. -0.29 (−0.75–0.16), p = 0.0002) but negatively affected ApoB concentrations (0.05 (−0.01–0.11) vs. 0.03 (−0.07–0.00), p = 0.0004) and ApoB/A1 ratio (0.01 (−0.03–0.05) vs. −0.02 (−0.04–0.00), p = 0.0113). No differences between the other analyzed parameters were observed. In conclusion, amaranth oil does not have a greater beneficial effect on atherosclerosis markers than rapeseed oil. However, further studies with a longer intervention period are needed. The study was retrospectively registered with the German Clinical Trials Register within the number: DRKS00014046, date of registration: 3 May 2018.

2021 ◽  
Francesco Fantin ◽  
Mazzali Gloria ◽  
Rizzatti Vanni ◽  
Zoico Elena ◽  
Rossi Andrea ◽  

Abstract Purpose: Accumulation of epicardial adipose tissue (EAT) is associated with severity and progression of coronary artery disease (CAD). The aim of this study was to compare EAT fibrosis, inflammation, Hypoxia-inducible factor 1-alpha (HIF1-α) and caveolin-1 (CAV-1) between subjects with and without CAD.Methods and Results: Body mass index (BMI), waist circumference (WC), glucose, insulin, homeostasis model assessment index, serum leptin and adiponectin were evaluated in EAT of patients with and without CAD undergoing elective surgery. Biopsies were collected from EAT. Immunohistochemistry for macrophages CD68, CD11c, CD163, HIF1-α and CAV-1 was performed and Masson Trichrome staining to define the degree of fibrosis.A total of 22 male patients (age range from 51-80 years), were studied: 12 CAD and 10 non-CAD undergoing elective surgery.Fibrosis, HIF1-α, number of total CD68, CD163 and CD11c were higher in CAD than in non-CAD patients, whilst serum adiponectin and CAV-1 significantly lower. In 4 patients with CAD, but in none in those without, macrophages aggregated in crown like structure were found. Fibrosis correlated with HIF1-α and M1 pro-inflammatory CD11c (+) macrophages; HIF1-α with total, M1 pro-inflammatory CD11c (+) and M2 anti-inflammatory CD163 (+) macrophages; Caveolin-1 positively correlated with serum adiponectin.Conclusions: CAD patients displays a dysfunctional EAT characterized by greater inflammation, fibrosis, HIF1-α and lower CAV. Our results seem to suggest that adiponectin may decline CAD risk even by determining an increase of CAV-1. Level of evidence: III cross-sectional study.

2021 ◽  
Timm Amendt ◽  
Gabriele Allies ◽  
Antonella Nicolo ◽  
Omar El Ayoubi ◽  
Marc Young ◽  

Homeostasis of metabolism by hormone production is crucial to maintain physiological integrity and disbalance can cause severe metabolic disorders such as diabetes mellitus. Here, we show that antibodies recognizing insulin are key regulators of blood glucose and metabolism controlling insulin concentrations. In fact, antibody-deficient mice and immunodeficiency patients show sub-physiological blood glucose, which becomes normal after total IgG injection. We show that insulin-specific IgG antibodies found in the serum of wildtype mice or healthy individuals are responsible for this regulation. Interestingly, we identify two fractions of anti-insulin IgM which differ in their affinity to insulin. The low affinity IgM fraction (anti-insulin IgMlow) neutralizes insulin and leads to increased blood glucose while the high affinity IgM fraction (anti-insulin IgMhigh) protects insulin from neutralization by anti-insulin IgG thereby preventing blood glucose dysregulation. In contrast to anti-insulin IgMhigh, anti-insulin IgMlow binds to dsDNA suggesting that it is multi-specific. This multi-specificity mediates the formation of larger immune complexes containing insulin which results in increased uptake and degradation of insulin by macrophages in the presence of anti-insulin IgMlow as compared to anti-insulin IgMhigh. To demonstrate that high affinity anti-insulin IgM acts as protector of insulin and counteracts insulin neutralization by anti-insulin IgG, we expressed the variable regions of the same anti-insulin antibody as IgG or IgM. Strikingly, only the anti-insulin IgM regulated insulin function and prevented IgG-mediated neutralization of insulin and subsequent blood glucose dysregulation. Since anti-insulin IgMhigh is generated in the course of an immune response and affinity maturation, its protective role suggests that preventing autoimmune damage and maintaining physiological homeostasis requires adaptive tolerance mechanisms that generate protective IgM antibodies during memory responses.

Amr Ali El-Sehrawy ◽  
Enas M Elkhamisy ◽  
Amani E Badawi ◽  
Heba A Elshahawy ◽  
Eman Elsayed ◽  

Background: Considering the vital role of vascular endothelial growth factor (VEGF) in the development of diabetic retinopathy (DR) in one hand and the frequent association between subclinical hypothyroidism (SCH) and DR on the other hand. Objective: The present study was proposed to explore the possible role of VEGF in the relation between SCH and DR, thus we investigated the relation between SCH and VEGF levels in patients with DR. Methods: Two hundred patients with DR were recruited in this study [100 patients with proliferative diabetic retinopathy (PDR) and 100 patients with non-proliferative diabetic retinopathy (NPDR)]. Patients with DR were divided into 2 groups according to thyroid function: patients with SCH or those with euthyroidism. Patients were subjected to careful history taking, and underwent clinical and ophthalmological examination. Fasting blood glucose, glycosylated hemoglobin, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), TSH, FT4, FT3, VEGF and thyroid volume were assessed Results: Among all the studied patients, 21.5% (43/200) had SCH. DR patients with SCH had higher age, diabetes duration, HbA1c, HOMA-IR and VEGF than those with euthyroidism. The frequency of PDR in patients with SCH was 72.1% (31/43) and 43.9% (69/157) in those with euthyroidism, whereas the frequency of NPDR in patients with SCH was 27.9 (12/43) and 56.1% (88/157) in those with euthyroidism (P < 0.003). In multivariate analysis, PDR, HOMA-IR and VEGF levels were the significant predictor variables of SCH. Conclusions: Increased VEGF levels may be implicated in the relationship between SCH and DR.

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