scholarly journals New Mammalian Glycerol-3-Phosphate Phosphatase: Role in β-Cell, Liver and Adipocyte Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Elite Possik ◽  
Anfal Al-Mass ◽  
Marie-Line Peyot ◽  
Rasheed Ahmad ◽  
Fahd Al-Mulla ◽  
...  

Cardiometabolic diseases, including type 2 diabetes, obesity and non-alcoholic fatty liver disease, have enormous impact on modern societies worldwide. Excess nutritional burden and nutri-stress together with sedentary lifestyles lead to these diseases. Deranged glucose, fat, and energy metabolism is at the center of nutri-stress, and glycolysis-derived glycerol-3-phosphate (Gro3P) is at the crossroads of these metabolic pathways. Cellular levels of Gro3P can be controlled by its synthesis, utilization or hydrolysis. The belief that mammalian cells do not possess an enzyme that hydrolyzes Gro3P, as in lower organisms and plants, is challenged by our recent work showing the presence of a Gro3P phosphatase (G3PP) in mammalian cells. A previously described phosphoglycolate phosphatase (PGP) in mammalian cells, with no established physiological function, has been shown to actually function as G3PP, under physiological conditions, particularly at elevated glucose levels. In the present review, we summarize evidence that supports the view that G3PP plays an important role in the regulation of gluconeogenesis and fat storage in hepatocytes, glucose stimulated insulin secretion and nutri-stress in β-cells, and lipogenesis in adipocytes. We provide a balanced perspective on the pathophysiological significance of G3PP in mammals with specific reference to cardiometabolic diseases.

2020 ◽  
pp. 19-24
Author(s):  
Yu. Kokovina ◽  
E. Yu. Pavlova ◽  
E. A. Antonova

Introduction. Today, non-alcoholic fatty liver disease (NAFLD) is increasingly associated with the presence or risk of developing type 2 diabetes (D2). The term “hepatogenic diabetes”, proposed to refer to SD2 in patients with cirrhosis of the liver (CP), has acquired a new meaning, since this combination is of growing interest. The authors analyzed the current literature and summarized data on the pathogenesis, risk factors, and possible therapy of NAFLD.Objective: to evaluate the effectiveness of L-ornithine-L-aspartate (HEPA-Merz, Merz Pharma GmbH & Co) in combination with biguanides in the treatment of NAFLD patients in combination with D2.Materials and methods. The study included 30 patients aged 26 to 60 years with a verified diagnosis of NAFLD of varying degrees of activity in combination with D2. All patients were prescribed combination therapy with the drug HEPA-Merz (“Merz Pharma GmbH and Co”) at a dose of 3 grams 3 times a day in combination with biguanides. The examination was performed on the 1st, 28-th and 56-th days of treatment. In order to determine the effectiveness of therapy, we evaluated the dynamics of clinical symptoms (asthenovegetative, dyspeptic syndromes, pain syndrome in the ball system), biochemical parameters of liver function (changes in markers of cytolysis, cholestasis), lipidogram indicators, glucose levels, glycated hemoglobin, and ultrasound results of abdominal organs.Results. On day 56, asthenovegetative, dyspeptic and pain syndrome were stopped during therapy. Most patients showed a decrease in body weight from 3 to 5 kg. When evaluating changes in biochemical parameters on the 28-th day, the activity of ALT, AST, GGTP and glucose levels significantly decreased against the background of the therapy. On the 56th day of treatment, the activity of transaminases, bilirubin, GGTP and GFR in all patients were within the reference values.Conclusion. Understanding the multifactorial nature of NAFLD and the mechanisms of associated diseases, including D2, will allow us to assess the prognosis of the disease and prescribe adequate timely therapy. The effectiveness of the original ornithineaspartate (Merz Pharma GmbH & Co.) is manifested by a decrease in the processes of cytolysis of hepatocytes, normalization of lipid and carbohydrate metabolism.


2016 ◽  
Vol 25 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Andrea Fialho ◽  
Andre Fialho ◽  
Prashanthi Thota ◽  
Arthur J. McCullough ◽  
Bo Shen

Background: Changes in gut bacteria play a role in type 2 diabetes mellitus (DM) and hepatic steatosis. There is a lack of studies evaluating the frequency and risk factors for non-alcoholic fatty liver disease (NAFLD) in patients tested for small intestinal bacterial overgrowth (SIBO). Aim: To evaluate the frequency of NAFLD and associated risk factors in patients tested for SIBO. Methods: In this case-control study, 372 eligible patients submitted to glucose hydrogen/methane breath test for SIBO who also had an abdominal imaging study were included. Patients were divided into SIBO-positive and SIBO-negative groups. Clinical, demographic and laboratory variables were evaluated in addition to the presence of NAFLD on abdominal imaging. Results: Of the 372 eligible patients, 141 (37.9%) were tested positive for SIBO (study group) and 231 (62.1%) were negative for it (control group). NAFLD occurred in 45.4% (64/141) of the study group compared to 17.3% (40/231) of the control group (p<0.001). Patients in the study group were found to have higher rates of elevated aspartate aminotransferase (AST) (20.6% vs. 11.3%; p=0.034) and alanine aminotransferase (ALT) levels (56.0% vs. 40.7%; p= 0.039), type 2 diabetes (23.4% vs. 13.9%; p=0.041), hypertension (54.6% vs. 40.3%; p=0.046) and metabolic syndrome (78.0% vs. 60.2%; p=0.020). In the multivariate analysis, SIBO (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.14-3.31; p=0.014), type 2 DM (OR: 3.04; 95%CI: 1.57-5.90; p=0.001) and obesity (OR: 3.58; 95%CI: 1.70-7.54; p=0.001) remained associated with NAFLD.Conclusion: Patients with SIBO have an increased risk for hepatic steatosis and may benefit from aggressive control of the risk factors for NAFLD including metabolic syndrome. Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; CTE: computed tomography enterography; DM: diabetes mellitus; ETOH: ethanol; IL: interleukin; LPS: lipopolysaccharide; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PPI: proton pump inhibitor; SIBO: small intestinal bacterial overgrowth; TLR-4: toll-like receptor 4; TMAO: trimethylamine-N-oxide (TMAO); TNF-α: tumor necrosis factor alpha.


2021 ◽  
Vol 12 ◽  
pp. 204201882110002
Author(s):  
Taeang Arai ◽  
Masanori Atsukawa ◽  
Akihito Tsubota ◽  
Shigeru Mikami ◽  
Hiroki Ono ◽  
...  

Background: Although sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve not only glycemic control but also liver inflammation and fatty changes in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), its sustainability and effect on liver fibrosis have remained unclear. The current study aimed to clarify the effects of 48-week SGLT2-I therapy on liver inflammation, fatty changes, and fibrosis in NAFLD patients with T2DM. Methods: This study evaluated the effects of SGLT2-I on NAFLD, including liver fibrosis assessed via transient elastography, in 56 patients with NAFLD who received SGLT2-I for 48 weeks. Moreover, changes in each clinical parameter between patients receiving SGLT2-I (the SGLT2-I group) and those receiving other oral hypoglycemic agents (OHAs) (the non-SGLT2-I group) were compared, using 1:1 propensity score matching to adjust for baseline factors. Results: The SGLT2-I group exhibited a significant decrease in controlled attenuation parameter (312 dB/m at baseline to 280 dB/m at week 48) and liver stiffness measurement (9.1–6.7 kPa) ( p < 0.001 for both). After propensity score matching (44 patients each in the SGLT2-I and non-SGLT2-I groups), no significant difference in HbA1c decrease was observed between the two groups. However, compared with the non-SGLT2-I group, the SGLT2-I group showed a significant decrease in body weight ( p < 0.001), alanine aminotransferase ( p = 0.02), uric acid ( p < 0.001), and Fibrosis-4 (FIB-4) index ( p = 0.01) at week 48. The improvement in FIB-4 index, defined as a ⩾10% decline from baseline at week 48, was 56.8% (25/44) in the SGLT2-I group and 20.5% (9/44) in the non-SGLT2-I group ( p < 0.001). Conclusion: SGLT2-Is improved not only glycemic control but also liver fatty infiltration and fibrosis in patients with NAFLD and T2DM, suggesting their possible superiority to other OHAs concerning these effects.


Author(s):  
Susrichit Phrueksotsai ◽  
Kanokwan Pinyopornpanish ◽  
Juntima Euathrongchit ◽  
Apinya Leerapun ◽  
Arintaya Phrommintikul ◽  
...  

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