mRNA Expression of IGF-1 and IGF-1R in Patients with Colorectal Adenocarcinoma and Type 2 Diabetes

To characterize effects of type 2 diabetes (T2D) on mRNA expression levels for 10 Cytochromes P450 (CYP450s), two carboxylesterases, and three drug transporters (ABCB1, ABCG2, SLCO2B1) in human duodenal biopsies. To compare drug metabolizing enzyme activities of four CYP450 isoenzymes in duodenal biopsies from patients with or without T2D. mRNA levels were quantified (RT-qPCR) in human duodenal biopsies obtained from patients with (n = 20) or without (n = 16) T2D undergoing a scheduled gastro-intestinal endoscopy. CYP450 activities were determined following incubation of biopsy homogenates with probe substrates for CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2J2 (ebastine), and CYP3A4/5 (midazolam). Covariables related to inflammation, T2D, demographic, and genetics were investigated. T2D had no major effects on mRNA levels of all enzymes and transporters assessed. Formation rates of metabolites (pmoles mg protein−1 min−1) determined by LC-MS/MS for CYP2C9 (0.48 ± 0.26 vs. 0.41 ± 0.12), CYP2J2 (2.16 ± 1.70 vs. 1.69 ± 0.93), and CYP3A (5.25 ± 3.72 vs. 5.02 ± 4.76) were not different between biopsies obtained from individuals with or without T2D (p > 0.05). No CYP2B6 specific activity was measured. TNF-α levels were higher in T2D patients but did not correlate with any changes in mRNA expression levels for drug metabolizing enzymes or transporters in the duodenum. T2D did not modulate expression or activity of tested drug metabolizing enzymes and transporters in the human duodenum. Previously reported changes in drug oral clearances in patients with T2D could be due to a tissue-specific disease modulation occurring in the liver and/or in other parts of the intestines.

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Serum Concentrations and Subcutaneous Adipose Tissue mRNA Expression of Omentin in Morbid Obesity and Type 2 Diabetes Mellitus: the Effect of Very-Low-Calorie Diet, Physical Activity and Laparoscopic Sleeve Gastrectomy

Physiological Research ◽

10.33549/physiolres.932530 ◽

2014 ◽

pp. 207-218 ◽

Cited By ~ 7

Author(s):

M. URBANOVÁ ◽

I. DOSTÁLOVÁ ◽

P. TRACHTA ◽

J. DRÁPALOVÁ ◽

P. KAVÁLKOVÁ ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Mrna Expression ◽

Subcutaneous Adipose Tissue ◽

Very Low Calorie Diet ◽

Low Calorie Diet ◽

Calorie Diet ◽

Subcutaneous Adipose

Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omentin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omentin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and were positively related to HDL-cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight.

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Periodontal CD14 mRNA expression is downregulated in patients with chronic periodontitis and type 2 diabetes

BMC Oral Health ◽

10.1186/s12903-015-0118-3 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 1

Author(s):

Dustin C. Hedgpeth ◽

Xiaoming Zhang ◽

Junfei Jin ◽

Renata S. Leite ◽

Joe W. Krayer ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mrna Expression ◽

Chronic Periodontitis ◽

Cd14 Mrna

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Genistein and Momordica charantia L. prevents oxidative stress and upregulate proglucagon and insulin receptor mRNA in diabetic rats.

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2021-0378 ◽

2021 ◽

Author(s):

Wusa Makena ◽

Abdullahi Ibrahim Iliya ◽

Joseph Olajide Hambolu ◽

James Abrak Timbuak ◽

Uduak Emmanuel Umana ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Insulin Receptor ◽

Mrna Expression ◽

Insulin Signaling ◽

Diabetic Rats ◽

Momordica Charantia ◽

Receptor Mrna ◽

Group I

Type 2 diabetes (T2D) occur as a result of insulin resistance and malfunction in insulin signaling. Controlling hyperglycemia and activation of insulin signaling are important in the management of T2D. The study aimed to evaluate the effect of Genistein and Momordica charantia L. fruit on oxidative stress, markers of inflammation, and their role on proglucagon and insulin receptor mRNA expression by RT-PCR in diabetic rats. Thirty-five albino rats were divided into seven groups (n=5). Group I (non-diabetic) and group II (diabetic control) were treated with distilled water, groups III and IV received 250mg/kg and 500mg/kg lyophilized MCF respectively. Groups V and VI received 10mg/kg and 20mg/kg Genistein respectively while group VII received 500mg/kg Metformin. The administration lasted for 28 days. MCF and Genistein significantly reduced IL-1β and TNFα levels that was elevated in serum of diabetic rats. Treatment with MCF and Genistein significant increased the expression of proglucagon mRNA in the small intestine and insulin receptor mRNA in the liver of diabetic rats. In conclusion, MCF and Genistein ameliorate type 2 diabetes complications by preventing the loss of insulin-positive cells, inhibiting IL-1β and TNFα and up-regulating proglucagon and insulin receptor mRNA expression. Novelty: • MCF and Genistein has an inhibitory effect on diabetic induced IL-1β and TNFα production. • MCF and Genistein up-regulates proglucagon and insulin receptor mRNA expression.

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Reduction of Insulin Signaling Upregulates Angiopoietin-like Protein 4 Through Elevated Free Fatty Acids in Diabetic Mice

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0031-1291258 ◽

2011 ◽

Vol 120 (03) ◽

pp. 139-144 ◽

Cited By ~ 16

Author(s):

N. Mizutani ◽

N. Ozaki ◽

Y. Seino ◽

A. Fukami ◽

E. Sakamoto ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Adipose Tissue ◽

Mrna Expression ◽

High Fat Diet ◽

Serum Triglyceride ◽

Diabetic Mice ◽

Brown Adipose

AbstractAngiopoietin-like protein 4 (Angptl4) is thought to cause an increase in serum triglyceride levels. In the present study, we elucidated Angptl4 expression in the mouse models of type 1 and type 2 diabetes mellitus, and investigated the possible mechanisms involved.Type 1 diabetes was induced in C57BL/6 J mice by treating them with streptozotocin (STZ). Type 2 diabetes was induced by feeding the mice a high-fat diet (HFD) for 18 weeks.The levels of Angptl4 mRNA expression in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) were found to increase in the STZ diabetic mice relative to control mice. This effect was attenuated by insulin administration. In the HFD diabetic mice, the Angptl4 mRNA expression levels were increased in liver, WAT, and BAT. Treatment with metformin for 4 weeks attenuated the increased levels of Angptl4 mRNA. Fatty acids (FAs) such as palmitate and linoleate induced Angptl4 mRNA expression in H4IIE hepatoma cells and 3T3-L1 adipocytes. Treatment with insulin but not metformin attenuated FA-induced Angptl4 mRNA expression in H4IIE. Both insulin and metformin did not influence the effect of FAs in 3T3-L1 cells.These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.

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LMNA mRNA Expression Is Altered in Human Obesity and Type 2 Diabetes

Obesity ◽

10.1038/oby.2008.276 ◽

2008 ◽

Vol 16 (8) ◽

pp. 1742-1748 ◽

Cited By ~ 14

Author(s):

Merce Miranda ◽

Matilde R. Chacón ◽

Cristina Gutiérrez ◽

Nuria Vilarrasa ◽

Jose M. Gómez ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mrna Expression ◽

Human Obesity

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Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00560.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. E1049-E1057 ◽

Cited By ~ 64

Author(s):

Sébastien L. Ménard ◽

Etienne Croteau ◽

Otman Sarrhini ◽

Roselle Gélinas ◽

Pascal Brassard ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acid ◽

Mrna Expression ◽

Oxidative Metabolism ◽

Left Ventricular ◽

Glucose Clamp ◽

Left Ventricular Ejection ◽

Myocardial Oxidative Metabolism

The purpose of this study was to determine in vivo myocardial energy metabolism and function in a nutritional model of type 2 diabetes. Wistar rats rendered insulin-resistant and mildly hyperglycemic, hyperinsulinemic, and hypertriglyceridemic with a high-fructose/high-fat diet over a 6-wk period with injection of a small dose of streptozotocin (HFHFS) and control rats were studied using micro-PET (μPET) without or with a euglycemic hyperinsulinemic clamp. During glucose clamp, myocardial metabolic rate of glucose measured with [18F]fluorodeoxyglucose ([18F]FDG) was reduced by ∼81% ( P < 0.05), whereas myocardial plasma nonesterified fatty acid (NEFA) uptake as determined by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) was not significantly changed in HFHFS vs. control rats. Myocardial oxidative metabolism as assessed by [11C]acetate and myocardial perfusion index as assessed by [13N]ammonia were similar in both groups, whereas left ventricular ejection fraction as assessed by μPET was reduced by 26% in HFHFS rats ( P < 0.05). Without glucose clamp, NEFA uptake was ∼40% lower in HFHFS rats ( P < 0.05). However, myocardial uptake of [18F]FTHA administered by gastric gavage was significantly higher in HFHFS rats ( P < 0.05). These abnormalities were associated with reduced Glut4 mRNA expression and increased Cd36 mRNA expression and mitochondrial carnitine palmitoyltransferase 1 activity ( P < 0.05). HFHFS rats display type 2 diabetes complicated by left ventricular contractile dysfunction with profound reduction in myocardial glucose utilization, activation of fatty acid metabolic pathways, and preserved myocardial oxidative metabolism, suggesting reduced myocardial metabolic efficiency. In this model, increased myocardial fatty acid exposure likely occurs from circulating triglyceride, but not from circulating plasma NEFA.

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The Effect of Very-Low-Calorie Diet on mRNA Expression of Inflammation-Related Genes in Subcutaneous Adipose Tissue and Peripheral Monocytes of Obese Patients with Type 2 Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-1858 ◽

2011 ◽

Vol 96 (4) ◽

pp. E606-E613 ◽

Cited By ~ 40

Author(s):

M. Mraz ◽

Z. Lacinova ◽

J. Drapalova ◽

D. Haluzikova ◽

A. Horinek ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Mrna Expression ◽

Obese Patients ◽

Very Low Calorie Diet ◽

Low Calorie Diet ◽

Calorie Diet ◽

Proinflammatory Factors

Abstract Context: Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. Objective: To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention. Design: Two-week intervention study with very-low-calorie diet (VLCD). Setting: University hospital. Patients: Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females. Intervention: Two weeks of VLCD (2500 kJ/d). Main Outcome Measures: Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM. Results: Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT. Conclusion: Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.

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