Sevda Gheibi1, Sajad Jeddi2, Mattias Carlström3, Khosrow Kashfi4, Asghar Ghasemi5. 1. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Neurophysiology Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 4. Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, USA; Graduate Program in Biology, City University of New York Graduate Center, New York, USA. Electronic address: kashfi@med.cuny.edu. 5. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Ghasemi@endocrine.ac.ir.
Abstract
OBJECTIVE: Decreased nitric oxide (NO) bioavailability and hydrogen sulfide (H2S) deficiency have been linked with the pathophysiology of type 2 diabetes (T2D). Restoration of NO levels by nitrite have been associated with favorable metabolic effects in T2D. Moreover, H2S can potentiate the effects of NO in the cardiovascular system. The aim of this study was to determine the effects of long-term co-administration of sodium nitrite and sodium hydrosulfide (NaSH) on carbohydrate metabolism in type 2 diabetic rats. METHODS: T2D was induced using chronic high fat diet (HFD) feeding combined with low dose streptozotocin (STZ) regimen. Rats were divided into 5 groups (N = 10/group): Control, T2D, T2D + nitrite, T2D + NaSH, and T2D + nitrite + NaSH. Nitrite (50 mg/L in drinking water) and NaSH (0.28 mg/kg, daily i. p. injection) were administered for 9 weeks. Fasting serum glucose, insulin, lipid profile, liver function tests, and oxidative stress indices were measured. Intraperitoneal glucose tolerance test (GTT) was performed at the end of the eighth week, and three days later, intraperitoneal pyruvate tolerance test (PTT) was done. Protein levels and mRNA expression of glucose transporter type 4 (GLUT4) in soleus muscle and epididymal adipose tissue as well as mRNA expression of H2S-producing enzymes in the liver, soleus muscle, and epididymal adipose tissue were measured at the end of the study. RESULTS: Compared to the controls, HFD and STZ treated rats developed metabolic dysfunction. Nitrite treatment improved carbohydrate metabolism, liver function, and oxidative stress indices whereas NaSH treatment per se had no significant effects. However, co-administration of NaSH and nitrite resulted in further improvement in serum insulin level, GTT, PTT, liver function, oxidative stress, protein level and mRNA expression of GLUT4, as well as mRNA expression of H2S-producing enzymes in diabetic rats. CONCLUSION: Low dose of NaSH per se had no effect on carbohydrate metabolism while it potentiated the favorable metabolic effects of inorganic nitrite in type 2 diabetic rats. These favorable effects were associated with decreased oxidative stress and increased GLUT4 expression in insulin-sensitive tissues as well as improvement of liver function.
OBJECTIVE: Decreased nitric oxide (NO) bioavailability and hydrogen sulfide (H2S) deficiency have been linked with the pathophysiology of type 2 diabetes (T2D). Restoration of NO levels by nitrite have been associated with favorable metabolic effects in T2D. Moreover, H2S can potentiate the effects of NO in the cardiovascular system. The aim of this study was to determine the effects of long-term co-administration of sodium nitrite and sodium hydrosulfide (NaSH) on carbohydrate metabolism in type 2 diabeticrats. METHODS: T2D was induced using chronic high fat diet (HFD) feeding combined with low dose streptozotocin (STZ) regimen. Rats were divided into 5 groups (N = 10/group): Control, T2D, T2D + nitrite, T2D + NaSH, and T2D + nitrite + NaSH. Nitrite (50 mg/L in drinking water) and NaSH (0.28 mg/kg, daily i. p. injection) were administered for 9 weeks. Fasting serum glucose, insulin, lipid profile, liver function tests, and oxidative stress indices were measured. Intraperitoneal glucose tolerance test (GTT) was performed at the end of the eighth week, and three days later, intraperitoneal pyruvate tolerance test (PTT) was done. Protein levels and mRNA expression of glucose transporter type 4 (GLUT4) in soleus muscle and epididymal adipose tissue as well as mRNA expression of H2S-producing enzymes in the liver, soleus muscle, and epididymal adipose tissue were measured at the end of the study. RESULTS: Compared to the controls, HFD and STZ treated rats developed metabolic dysfunction. Nitrite treatment improved carbohydrate metabolism, liver function, and oxidative stress indices whereas NaSH treatment per se had no significant effects. However, co-administration of NaSH and nitrite resulted in further improvement in serum insulin level, GTT, PTT, liver function, oxidative stress, protein level and mRNA expression of GLUT4, as well as mRNA expression of H2S-producing enzymes in diabeticrats. CONCLUSION: Low dose of NaSH per se had no effect on carbohydrate metabolism while it potentiated the favorable metabolic effects of inorganic nitrite in type 2 diabeticrats. These favorable effects were associated with decreased oxidative stress and increased GLUT4 expression in insulin-sensitive tissues as well as improvement of liver function.
Authors: Yu G Birulina; V V Ivanov; E E Buyko; I O Gabitova; I V Kovalev; A V Nosarev; L V Smagliy; S V Gusakova Journal: Bull Exp Biol Med Date: 2021-09-20 Impact factor: 0.804