Effects of Metformin and Sitagliptin Monotherapy on Expression of
                    Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat
                    Model of Type 2 Diabetes

Zhang, Minchun; Feng, Rilu; Yue, Jiang; Qian, Cheng; Yang, Mei; Liu, Wei; Rayner, Christopher K.; Ma, Jing

doi:10.1055/a-1135-9031

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…Expressions of SGLT1 in intestine and pancreas were reduced by metformin as well. A recent publication reported in kidney of Zucker Diabetic Fatty diabetic rats, the mRNA levels of SGLT1 and SGLT2 were downregulated by metformin [24], which is consistent with our results. In contrast, we found fluoxetine increased abundances of SGLT2 and SGLT1 in kidney of HFD mice, but decreased SGLT1 expression in intestine.…”

Section: Discussionsupporting

confidence: 94%

Potential impacts of diabetes mellitus and anti-diabetes agents on expressions of sodium-glucose transporters (SGLTs) in mice

Liao

Wang

et al. 2021

Endocrine

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Purpose Sodium-glucose transporters (SGLTs) are important targets for therapeutic intervention of type 2 diabetes. This study aims to evaluate the physiological influences of diabetes mellitus and the potential impacts of metformin and fluoxetine on SGLTs expressions. Methods Alterations of SGLT1 and SGLT2 were measured in organs involved in glucose homeostasis (kidney, intestine, liver and pancreas) of streptozotocin (STZ) and high-fat diet (HFD) induced diabetic mice by western blotting and real-time PCR (RT-PCR) respectively. Results In kidney, duodenal segments of intestine, liver, and pancreas of HFD diabetic mice, expressions of SGLT2 were all elevated compared to control mice. The level of SGLT1 was significantly increased in intestine, but was decreased in pancreas. SGLT1 expression in kidney was unaffected, and SGLT1 was undetectable in hepatocytes. Similar results were obtained in STZ diabetic mice. More importantly, here we noticed metformin decreased levels of SGLT2 in kidney, intestine, and pancreas of HFD mice markedly. Expressions of SGLT1 in intestine and pancreas were reduced by metformin as well. In contrast, fluoxetine increased abundances of SGLT2 and SGLT1 in kidney of HFD mice, but decreased SGLT1 expression in intestine. Conclusions The present study provided evidence that expressions of SGLT1 and SGLT2 were significantly modulated by diabetes mellitus as well as by metformin and fluoxetine, which indicated the efficacy of SGLT2 inhibitors might be impacted by these factors.

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Section: Discussionsupporting

confidence: 94%

Potential impacts of diabetes mellitus and anti-diabetes agents on expressions of sodium-glucose transporters (SGLTs) in mice

Liao

Wang

et al. 2021

Endocrine

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“…Likewise, chronic treatment with metformin reduces nociception and cognitive dysfunction in high-fat diet-induced insulin resistance. This drug also decreases all metabolic changes induced by a high-fat diet in rodents (Pintana et al, 2012;Lennox et al, 2014;Muñoz-Arenas et al, 2020;Zhang et al, 2020). Interestingly, chronic treatment with metformin for 24 weeks improves cognitive performance, reduces depression and metabolic changes induces by type 2 diabetes in human beings (Guo et al, 2014;Ng et al, 2014).…”

Section: Cognitive Deficitsmentioning

confidence: 98%

Metformin: A Prospective Alternative for the Treatment of Chronic Pain

et al. 2020

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Metformin (biguanide) is a drug widely used for the treatment of type 2 diabetes. This drug has been used for 60 years as a highly effective antihyperglycemic agent. The search for the mechanism of action of metformin has produced an enormous amount of research to explain its effects on gluconeogenesis, protein metabolism, fatty acid oxidation, oxidative stress, glucose uptake, autophagy and pain, among others. It was only up the end of the 1990s and beginning of this century that some of its mechanisms were revealed. Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK). Two upstream kinases account for the physiological activation of AMPK: liver kinase B1 and calcium/ calmodulin-dependent protein kinase kinase 2. Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain. These studies have highlighted the efficacy of this drug in chronic pain, such as that from neuropathy, insulin resistance, diabetic neuropathy, and fibromyalgia-type pain. Mounting evidence indicates that chronic pain may induce anxiety, depression and cognitive impairment in rodents and humans. Interestingly, metformin is able to reverse some of these consequences of pathological pain in rodents. The purpose of this review was to analyze the current evidence about the effects of metformin in chronic pain and three of its comorbidities (anxiety, depression and cognitive impairment).

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Early Diagnosis through Estimation of Inflammatory Biomarkers and the Neuroprotective Role of Metformin in Diabetic Peripheral Neuropathy

Sri¹,

Orsu

2023

PCI- Approved-IJPSN

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Purpose: Diabetic peripheral neuropathy (DPN), a chronic neurological complication of type 2 diabetes mellitus (T2DM) with signs and symptoms of peripheral nerve dysfunction such as numbness, tingling or burning sensation, paresthesias etc. Several lacunae exist in relation to the cause and effect of DPN. Therefore diagnosis, as well as treatment of DPN remains unsatisfactory. The involvement of chronic low-grade inflammation in DPN is a rapidly emerging concept and therefore the present study adds weight to it. We estimated some of the biomarkers of inflammation which may be the early markers of DPN. This study is the earliest of its kind to correlate the biomarker levels with metformin, a drug less reported in terms of its anti-inflammatory and neuroprotective activity. Methods: After approval from the institutional human ethical committee, 90 patients attending the outpatient ward of a tertiary care hospital were included in the study. They were divided into two groups: M- group (patients on non metformin) and M+ group (patients on metformin). 5ml serum sample from each patient was processed for estimation of IL-1, IL-6, IL-8, TNF- α, INF- α, GMCSF and MCP-1 according to the manufacturer’s instructions on the commercially available ELISA kit. Metformin levels in the serum were estimated by HPLC. Data was put into statistical analysis. Results: Results showed that IL-1, IL-2, IL-6 and TNF- α were significantly higher in the M- group. The difference was statistically significant between the two groups. The level of biomarkers showed a negative correlation with drug levels in the initial 2m treatment with the drug but was not statistically significant. However, after 6m treatment with metformin the correlation was found to be of statistical significance. Conclusion: we conclude that these biomarkers can be work tested for their clinical utility to be used as diagnostic tools for early detection of DPN and short-term metformin treatment greatly benefits DPN patients. Longitudinal studies may be more insightful as to the long term neuroprotective action of metformin.

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Effects of Metformin and Sitagliptin Monotherapy on Expression of Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat Model of Type 2 Diabetes

Cited by 3 publications

References 47 publications

Potential impacts of diabetes mellitus and anti-diabetes agents on expressions of sodium-glucose transporters (SGLTs) in mice

Potential impacts of diabetes mellitus and anti-diabetes agents on expressions of sodium-glucose transporters (SGLTs) in mice

Metformin: A Prospective Alternative for the Treatment of Chronic Pain

Early Diagnosis through Estimation of Inflammatory Biomarkers and the Neuroprotective Role of Metformin in Diabetic Peripheral Neuropathy

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