Browsing by Author "Cvijovic, Goran (6507040974)"

Metformin is the most frequently used drug in treatment of type 2 diabetes, particularly in obese patients. One of the potential mechanisms for his beneficial metabolic effect is activation of AMP-activated protein kinase (AMPK). AMPK is one of the key players in regulation of energy homeostasis, especially in skeletal muscles, liver and adipose tissue. Exercise, adiponectin and leptin are some of the activators of this pathway stimulating increased glucose uptake by increased GLUT-4 translocation to plasma membrane. LKB1, the upstream kinase in this pathway, is the tumor suppressor expected to inhibit initiation/growth of tumors and the activator of phosphorylation of threonin-172 of AMPK. Thus, AMPK pathway is meeting point of biochemical pathways mediating energy homeostasis and those mediating suppression of tumor genesis. We may speculate that activation of AMPK using metformin will inhibit LKB1 sensitive tumor initiation/growth. In vitro studies have shown reduced basal proliferation rate as well as abolished stimulation of breast cancer cell line with IGF-I or insulin induced marked cell proliferation during incubation with metformin. A few clinical studies reported reduced incidence of neoplastic diseases in diabetic patients treated with metforminin in comparison to diet or other antidiabetic agents. In conclusion, we may speculate that metformin could have antineoplastic effect, especially in LKB1 sensitive tumors (breast, prostate, ovary). © 2009 Nova Science Publishers, Inc.

Metformin is considered, in conjunction with lifestyle modification, as a first-line treatment modality for type 2 diabetes mellitus (DM). Recently, several clinical studies have reported reduced incidence of neoplastic diseases in DM type 2 patients treated with metformin, as compared to diet or other antidiabetic agents. Moreover, in vitro studies have disclosed significant antiproliferative and proapoptotic effects of metformin on different types of cancer. Metformin acts by activating AMP-activated protein kinase (AMPK), a key player in the regulation of energy homeostasis. Moreover, by activating AMPK, metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) resulting in decreased cancer cell proliferation. Concomitantly, metformin induces activation of LKB1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK. These new encouraging experimental data supporting the anti-cancer effects of metformin urgently require further clinical studies in order to establish its use as a synergistic therapy targeting the AMPK/mTOR signaling pathway.

We explored the effect of therapeutic glucoregulation on the blood levels of proinflammatory T helper (Th)17 cytokines interleukin (IL)-17 and IL-23, and Th1 cytokines interferon (IFN)-γ and IL-12 in newly diagnosed type 2 diabetes patients. The investigated group consisted of 23 subjects (17 men and 6 women, age 26-64). The cytokine serum levels, glycated hemoglobin (HbA1c) as a marker of glucoregulation, homeostasis model assessment index as a measure of insulin resistance (HOMA-IR), and body mass index (BMI) were determined before and after 12 weeks of therapy consisting of standard lifestyle modification and metformin (1000. mg b.i.d.). The levels of Th17 and Th1 cytokines before treatment did not correlate with age, BMI or HOMA-IR. The patients with poor glucoregulation (HbA1c. >. 7%, n= 12), compared to those with good glucoregulation (HbA1c. ≤. 7%, n= 11), had higher serum levels of Th17 and Th1 cytokines, but only the differences in IL-17 (median 21.2. pg/ml vs. 4.8. pg/ml) and IFN-γ 5 (0.6. pg/ml vs. 27.7. pg/ml) reached statistical significance (p= 0.003 and p= 0.012, respectively). The reduction of HbA1c values (from 8.6 to 5.9%, p= 0.000) observed upon treatment in patients with poor glucoregulation was associated with a significant decrease in the concentration of IL-17 (from 21.2 to 12.9. pg/ml, p= 0.020), but not IFN-γ (50.6 vs. 52.3, p= 0.349). These data indicate that therapeutic improvement of glucoregulation might contribute to a reduction of IL-17 levels in newly diagnosed type 2 diabetes patients. © 2013 Elsevier GmbH.

We explored the effect of therapeutic glucoregulation on the blood levels of proinflammatory T helper (Th)17 cytokines interleukin (IL)-17 and IL-23, and Th1 cytokines interferon (IFN)-γ and IL-12 in newly diagnosed type 2 diabetes patients. The investigated group consisted of 23 subjects (17 men and 6 women, age 26-64). The cytokine serum levels, glycated hemoglobin (HbA1c) as a marker of glucoregulation, homeostasis model assessment index as a measure of insulin resistance (HOMA-IR), and body mass index (BMI) were determined before and after 12 weeks of therapy consisting of standard lifestyle modification and metformin (1000. mg b.i.d.). The levels of Th17 and Th1 cytokines before treatment did not correlate with age, BMI or HOMA-IR. The patients with poor glucoregulation (HbA1c. >. 7%, n= 12), compared to those with good glucoregulation (HbA1c. ≤. 7%, n= 11), had higher serum levels of Th17 and Th1 cytokines, but only the differences in IL-17 (median 21.2. pg/ml vs. 4.8. pg/ml) and IFN-γ 5 (0.6. pg/ml vs. 27.7. pg/ml) reached statistical significance (p= 0.003 and p= 0.012, respectively). The reduction of HbA1c values (from 8.6 to 5.9%, p= 0.000) observed upon treatment in patients with poor glucoregulation was associated with a significant decrease in the concentration of IL-17 (from 21.2 to 12.9. pg/ml, p= 0.020), but not IFN-γ (50.6 vs. 52.3, p= 0.349). These data indicate that therapeutic improvement of glucoregulation might contribute to a reduction of IL-17 levels in newly diagnosed type 2 diabetes patients. © 2013 Elsevier GmbH.