scholarly journals Genetic Determinants of Obesity Heterogeneity in Type II Diabetes

2020 ◽  
Author(s):  
Somayeh Alsadat Hosseini Khorami ◽  
Mohd Sokhini Abd Mutalib ◽  
Mohammad Feili Shiraz ◽  
Joseph Anthony Abdullah ◽  
Zulida Rejali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Molecular Mechanism ◽  
Type Ii Diabetes ◽  
Insulin Signalling ◽  
Diabetic Group ◽  
Akt Pathway ◽  
Type Ii ◽  
Fasting State ◽  
Significant Difference

Abstract Background: Although obesity is considered as the main cause of Type II diabetes (T2DM), non-obese individuals may still develop T2DM and obese individuals may not. Method: The mRNA expression of insulin signalling components (PI3K/AKT axis) from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism. Result: In present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics. Conclusion: The components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.

scholarly journals Genetic Determinants of Obesity Heterogeneity in Type II Diabetes

2020 ◽  
Author(s):  
Somayeh Alsadat Hosseini Khorami ◽  
Mohd Sokhini Abd Mutalib ◽  
Mohammad Feili Shiraz ◽  
Joseph Anthony Abdullah ◽  
Zulida Rejali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Molecular Mechanism ◽  
Type Ii Diabetes ◽  
Insulin Signalling ◽  
Gene Expression Pattern ◽  
Diabetic Group ◽  
Type Ii ◽  
Fasting State ◽  
Significant Difference

Abstract Background: Although obesity is considered as the main cause of Type II diabetes (T2DM), non-obese individuals may still develop T2DM and obese individuals may not. Method: The mRNA expression of PI3K/AKT axis from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism. Result: In present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups and were statistically significant. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics.Conclusion: The components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors, contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.

scholarly journals Gene Expression Pattern of PI3K/AKT Pathway Based on Insulin Resistance and Vitamin D Toward the Understanding of T2DM Pathogenesis

2020 ◽  
Author(s):  
Somayeh Alsadat Hosseini Khorami ◽  
Mohd Sokhini Abd Mutalib ◽  
Mohammad Feili Shiraz ◽  
Joseph Anthony Abdullah ◽  
Zulida Rejali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Vitamin D ◽  
Insulin Signalling ◽  
Serum Vitamin ◽  
Pten Expression ◽  
Expression Level ◽  
Akt Pathway ◽  
Serum Vitamin D ◽  
Significant Difference

Abstract Insulin-stimulated glucose transport occurs via PI3K/AKT -dependent pathway which results in GLUT4 translocation from intracellular vesicles to plasma membrane and glucose uptake. PTEN , as a phosphatase, is the main antagonist of the PI3K/AKT pathway’s kinases. Present study was performed to investigate underlying mechanism responsible for defects in insulin signalling, hence, RT-PCR was employed to investigate mRNA expression level of IRS1/PI3K/PDK1/AKT2/GLUT4/PTEN in diabetic and non-diabetic participants and serum vitamin D was measured by HPLC. Findings provide evidence that IRS1 gene expression was preserved while PI3K/PDK1/AKT2/GLUT4 were expressed significantly lower in diabetics compared to non-diabetics. Albeit there was no significant difference in PTEN expression between groups, PTEN was up-regulated by the years of having diabetes. As T2DM has been characterized by defects in insulin signalling at transcriptional level and post-translational modifications, it is difficult to conclude what exactly happens since only gene expression was considered, nevertheless it can be concluded that insulin resistance is not caused through an alteration in PTEN expression as a primary defect but may be caused by decreased PI3K/PDK1/AKT2/GLUT4 signalling and dysregulation of feedback loops. Particularly, PTEN expression showed a significant relation with duration of diabetes, suggesting that PTEN may not be the cause of the reduced expression of PI3K/AKT pathway in diabetes while it can be the effect of that. No significant correlations between serum vitamin D concentration and gene expression level of GOIs were observed in either group of participants which could be due to the non-linearity relationships as insulin signaling is a cascade with amplifying properties.

scholarly journals Association of fetuin-A with dyslipidemia and insulin resistance in type-II Diabetics of Pakistani population

2019 ◽  
Vol 36 (2) ◽  
Author(s):  
Fasiha Fatima ◽  
Naveed Ahsan ◽  
Aliya Nasim ◽  
Faiza Alam
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Lipid Profile ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Pakistani Population ◽  
Fetuin A ◽  
Significant Difference ◽  
Type Ii Diabetics

Background & Objective: Fetuin-A, hepatokine is responsible for instigating insulin resistance by inhibiting tyrosine kinase receptors. Our objective was to investigate the relationship of fetuin-A with dyslipidemia and insulin resistance in type-II diabetics of Pakistani population. Methods: In this cross sectional study which was conducted at Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi between October 2013 to March 2014, a total of 330 participants were selected and divided into two groups. Group-A (n = 165) normal healthy individual and Group-B (n = 165) Type-II diabetes mellitus mellitus with no comorbidities. Serum fetuin-A and insulin levels were determined by commercially prepared ELISA kits while fasting blood glucose (FBG) and lipid profile were performed by enzymatic kit method. Employing independent t-test, comparison of groups was done and correlation was achieved by using spearman correlation. Results: The results demonstrate a significant difference in mean values of fetuin-A, lipid profile, glucose, insulin and Homoeostasis Model Assessment of Insulin resistance (HOMA-IR) in type-II diabetics when compared to normal healthy individuals (p<0.01). A positive correlation was found between serum fetuin-A levels and FBG(r= 0.495, p< 0.001), insulin(r= 0.227, p< 0.001), HOMA-IR(r= 0.336, p<0.001, triglycerides(r= 0.197, p< 0.001) and LDL-cholesterol(r= 0.170, p= 0.002), while negative correlation with HDL-cholesterol(r= -0.251, p< 0.001). Conclusion: The study concludes that fetuin-A might be accountable for dyslipidemia and insulin resistance in type-II diabetes mellitus mellitus. So the high levels of Fetuin-A responsible for insulin resistance might alters endothelium and causes inflammation, vasoconstriction and thrombosis and ultimately atherosclerosis. doi: https://doi.org/10.12669/pjms.36.2.1106 How to cite this:Fatima F, Ahsan N, Nasim A, Alam F. Association of fetuin-A with dyslipidemia and insulin resistance in type-II Diabetics of Pakistani population. Pak J Med Sci. 2020;36(2):---------. doi: https://doi.org/10.12669/pjms.36.2.1106 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Comparison of Vibration Threshold of Upper Limb During Upper Limb Neurodynamic Test 1 in Individuals with and without Type II Diabetes Mellitus

2017 ◽  
Vol 3 (2) ◽  
pp. 79-86
Author(s):  
Ravi Shankar Reddy
Keyword(s):  
Diabetes Mellitus ◽  
Upper Limb ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Group ◽  
P Value ◽  
Type Ii ◽  
Significant Difference ◽  
Asymptomatic Individuals ◽  
Vibration Threshold

Background: Patients withType II diabetes mellitus are showed to affect the sensory, reflex and motor systems in distal extremities. Studies have examined the mechanosensitivity and vibration threshold (VT) in type II diabetes mellitus patients in the lower limb and compared it with normal individuals. There is scanty literature available in comparison of the VTin the upper limb in type II diabetes mellitus patients with non-diabetic individuals. Methods: Thirty type II diabetic individuals (age - 55.60 ± 9.79 years)and 30 asymptomatic individuals (age - 53.43±9.96) without diabetes mellitus participated in the study. Tester at the baseline for both the groups using a bioesthesiometer measured VT. Bioesthesiometer is capable of deriving a vibration of 100 Hz. Following VTevaluation at the baseline, the tester performed the ULNT1 for all the subjects. During the sequence of the ULNT1, VTwas measured at initial onset of pain (termed as P1) and short of maximum pain (P2) as experienced by the patient. Results:There was a statistical significant difference inVTbetween diabetic and non-diabetic group subjects. VTwas raised in the diabetic group at all the three levelsof evaluation (baseline, P1 and P2) compared to the non-diabetic group with a p value < 0.001. Conclusion: VT of the upper limb is higher in individuals with type II diabetes mellitus as compared to non-diabetic individuals.

scholarly journals Gene Expression of GSK3 in Type II Diabetics Compared to Non-Diabetics (ex vivo)

2020 ◽  
Vol 10 (1) ◽  
pp. 30-37
Author(s):  
Somayeh A.H. Khorami ◽  
Mohd S. Abd Mutalib ◽  
Mohammad F. Shiraz ◽  
Joseph A. Abdullah ◽  
Zulida Rejali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Glycogen Synthase ◽  
Ex Vivo ◽  
Glycogen Synthesis ◽  
Gene Expression Level ◽  
Expression Level ◽  
Type Ii ◽  
Cross Sectional ◽  
Significant Difference

Background: GSK3 is a serine/threonine kinase that is involved in the storage of glucose into glycogen through the negative regulation of glycogen synthase. Defects in GSK3 and glycogen synthase function are early stages of the development of insulin resistance, which may cause impaired glycogen synthesis in Type II diabetes. Methods: In this cross-sectional study, the gene expression level of GSK3 from Type II diabetic and non-diabetic participants was compared via real-time RT-PCR. To investigate the relationships between GSK3 expression and indicators of insulin resistance, Pearson's correlation analysis was performed. To compare the differences between GSK3 expression levels based on BMI categories, one-way ANOVA was used. Results: Gene expression of GSK3 was slightly higher in diabetic participants compared to non-diabetics, but it was statistically insignificant. Also, no significant difference was found based on BMI categories in the two groups. No significant association between GSK3 expression and indicators of insulin resistance was observed in non-diabetic participants. There was only a positive significant correlation between GSK3 expression and FBS in diabetic participants. Conclusion: These results indicate that the regulation of GSK3 may occur at the translation level, as gene expression level was unaltered between diabetic and non-diabetic participants. Also, since circulating levels of both glucose and insulin regulate GSK3 activity, tissue specificity for the expression and post-translation regulations of GSK3 may exist, which cause hyperactivation or overexpression in some target tissues in diabetes. Furthermore, it is probable that glycogen synthase activity is also regulated by non-insulin mediated mechanisms like exercise or allosteric changes, independent of GSK3 expression.

Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes

Diabetes ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1341-1350 ◽  
Author(s):  
J. P. Felber ◽  
E. Ferrannini ◽  
A. Golay ◽  
H. U. Meyer ◽  
D. Theibaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Oxidation ◽  
Type Ii Diabetes ◽  
Type Ii

scholarly journals Potent Natural Inhibitors of Alpha-Glucosidase and Alpha-Amylase against Hyperglycemia in Vitro and in Vivo

2017 ◽  
Author(s):  
Jirawat Riyaphan ◽  
Chien-Hung Jhong ◽  
May-Jwan Tsai ◽  
Der-Nan Lee ◽  
Max K. Leong ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Herbal Medicines ◽  
Alpha Amylase ◽  
Type Ii ◽  
Reference Drug ◽  
Significant Difference ◽  
Natural Inhibitors ◽  
Alpha Glucosidase

The inhibition of alpha-glucosidase and alpha-amylase is one of clinic strategies for remedy the type II diabetes. Herbal medicines are reported to alleviate hyperglycemia. However, the constituents from those sources whether are targeted to the alpha-glucosidase and alpha-amylase still unexplored. This study attempted to select the compounds for efficacy of hypoglycemia via cellular and mouse levels. The results illustrated that the cytotoxicity in all tested compounds at various concentrations except the concentration of 16-hydroxy-cleroda-3,13-dine-16,15-olide (HCD) at 30 &micro;M were not significant difference (p &gt; 0.05) when compared with the untreated control. Acarbose (reference drug), Antroquinonol, Catechin, Quercetin, Actinodaphnine, Curcumin, HCD, Docosanol, Tetracosanol, Berberine, and Rutin could effectively inhibit the alpha-glucosidase activity of Caco-2 cells when compared with the control (maltose). The compounds (Curcumin, HCD, Tetracosanol, Antroquinonol, Berberine, Catechin, Actinodaphnine, and Rutin) could reduce blood sugar level at 30 min in tested mice. The effects of tested compounds on area under curve (AUC) were significant (p &lt; 0.05) among Acarbose, Tetracosanol, Antroquinonol, Catechin, Actinodaphnine, and Rutin along with Berberine and Quercetin. In in vitro (alpha-glucosidase) with in vivo (alpha-amylase) experiments suggest that bioactive compounds can be a potential inhibitor candidate of alpha-glucosidase and alpha-amylase for the alleviation of type II diabetes.

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