scholarly journals Inhibition of 11β-HSD1 by LG13 improves glucose metabolism in type 2 diabetic mice

2015 ◽  
Vol 55 (2) ◽  
pp. 119-131 ◽  
Author(s):  
Leping Zhao ◽  
Yong Pan ◽  
Kesong Peng ◽  
Zhe Wang ◽  
Jieli Li ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Fasting Blood Glucose ◽  
Diabetic Mice ◽  
Insulin Sensitizer ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Type 2 Diabetic

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) controls the production of active glucocorticoid (GC) and has been proposed as a new target for the treatment of type 2 diabetes. We have previously reported that a natural product, curcumin, exhibited moderate inhibition and selectivity on 11β-HSD1. By analyzing the models of protein, microsome, cells and GCs-induced micein vitroandin vivo, this study presented a novel curcumin analog, LG13, as a potent selective 11β-HSD1 inhibitor.In vivo, Type 2 diabetic mice were treated with LG13 for 42 days to assess the pharmacological benefits of 11β-HSD1 inhibitor on hepatic glucose metabolism.In vitrostudies revealed that LG13 selectively inhibited 11β-HSD1 with IC50values at nanomolar level and high selectivity over 11β-HSD2. Targeting 11β-HSD1, LG13 could inhibit prednisone-induced adverse changes in mice, but had no effects on dexamethasone-induced ones. Further, the 11β-HSD1 inhibitors also suppressed 11β-HSD1 and GR expression, indicating a possible positive feedback system in the 11β-HSD1/GR cycle. In type 2 diabetic mice induced by high fat diet plus low-dosage STZ injection, oral administration with LG13 for 6 weeks significantly decreased fasting blood glucose, hepatic glucose metabolism, structural disorders, and lipid deposits. LG13 exhibited better pharmacological effectsin vivothan insulin sensitizer pioglitazone and potential 11β-HSD1 inhibitor PF-915275. These pharmacological and mechanistic insights on LG13 also provide us novel agents, leading structures, and strategy for the development of 11β-HSD1 inhibitors treating metabolic syndromes.

scholarly journals Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice

2019 ◽  
Vol 240 (2) ◽  
pp. 195-214 ◽  
Author(s):  
Te Du ◽  
Liu Yang ◽  
Xu Xu ◽  
Xiaofan Shi ◽  
Xin Xu ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Indole Alkaloid ◽  
Cerebrovascular Diseases ◽  
Diabetic Mice ◽  
Cell Protection ◽  
Madagascar Periwinkle ◽  
Type 2 Diabetic

Vincamine, a monoterpenoid indole alkaloid extracted from the Madagascar periwinkle, is clinically used for the treatment of cardio-cerebrovascular diseases, while also treated as a dietary supplement with nootropic function. Given the neuronal protection of vincamine and the potency of β-cell amelioration in treating type 2 diabetes mellitus (T2DM), we investigated the potential of vincamine in protecting β-cells and ameliorating glucose homeostasis in vitro and in vivo. Interestingly, we found that vincamine could protect INS-832/13 cells function by regulating G-protein-coupled receptor 40 (GPR40)/cAMP/Ca2+/IRS2/PI3K/Akt signaling pathway, while increasing glucose-stimulated insulin secretion (GSIS) by modulating GPR40/cAMP/Ca2+/CaMKII pathway, which reveals a novel mechanism underlying GPR40-mediated cell protection and GSIS in INS-832/13 cells. Moreover, administration of vincamine effectively ameliorated glucose homeostasis in either HFD/STZ or db/db type 2 diabetic mice. To our knowledge, our current work might be the first report on vincamine targeting GPR40 and its potential in the treatment of T2DM.

GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type 2 diabetic mice

2014 ◽  
Vol 127 (2) ◽  
pp. 91-100 ◽  
Author(s):  
Qian Wang ◽  
Ning Wang ◽  
Mei Dong ◽  
Fang Chen ◽  
Zhong Li ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Diabetic Mice ◽  
Hepatic Gluconeogenesis ◽  
Potential Therapeutic Target ◽  
Hepatocarcinoma Cells ◽  
Type 2 Diabetic

In the present study, we demonstrate that GdCl3 reduces hyperglycaemia via the Akt/FoxO1-induced suppression of hepatic gluconeogenesis, both in Type 2 diabetic mice (in vivo) and in hepatocarcinoma cells (in vitro), suggesting that GdCl3 may be a potential therapeutic target for diabetes.

scholarly journals Induction of adiponectin in skeletal muscle of type 2 diabetic mice: in vivo and in vitro studies

Diabetologia ◽  
2006 ◽  
Vol 49 (6) ◽  
pp. 1311-1323 ◽  
Author(s):  
A. M. Delaigle ◽  
M. Senou ◽  
Y. Guiot ◽  
M. -C. Many ◽  
S. M. Brichard
Keyword(s):  
Skeletal Muscle ◽  
In Vitro Studies ◽  
Diabetic Mice ◽  
Type 2 Diabetic

scholarly journals Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xing Zhang ◽  
Yihong Jiang ◽  
Qun Huang ◽  
Zhaoyu Wu ◽  
Hongji Pu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Limb Ischemia ◽  
Tube Formation ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Abstract Background Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. Methods ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson’s staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. Results The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel’s density than the ADSC-Exo and control groups by Masson’s staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, as well as the increased secretion of VEGF, IGF-1, and FGF. Conclusion Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.

scholarly journals Exosomes derived from adipose-derived stem cells overexpressing Glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia

2021 ◽  
Author(s):  
Xing Zhang ◽  
Yihong Jiang ◽  
Qun Huang ◽  
Zhaoyu Wu ◽  
Hongji Pu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Limb Ischemia ◽  
Tube Formation ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Abstract Background: Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics.Methods: ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted ADSCs (G-ADSC-Exos) were isolated and characterized to co-culture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson’s staining, immunofluorescence and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored.Results: The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel’s density than the ADSC-Exo and control groups by Masson’s staining, and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, as well as the increased secretion of VEGF, IGF-1, and FGF.Conclusion: Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.

scholarly journals Fermented Rice Germ Extract Ameliorates Abnormal Glucose Metabolism via Antioxidant Activity in Type 2 Diabetes Mellitus Mice

2021 ◽  
Vol 11 (7) ◽  
pp. 3091
Author(s):  
Ye Ji Hyun ◽  
Ju Gyeong Kim ◽  
Sung Keun Jung ◽  
Ji Yeon Kim
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Ferulic Acid ◽  
Fasting Blood Glucose ◽  
Liver Weight ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Abnormal Glucose Metabolism ◽  
Hepatic Glucose

Rice germ is an abundant source of ferulic acid, which is known for its anti-oxidant activity. This study aimed to evaluate the regulatory effects of fermented rice germ extracts on hepatic glucose metabolism in C57BL/KsJ-db/db mice. Rice germ was fermented with Lactobacillus plantarum and extracted with 30% ethanol (RG_30E) or 50% ethanol (RG_50E). Mice were fed modified AIN-93 diets containing fermented rice germ extracts and ferulic acid for 8 weeks. RG_50E significantly reduced food intake as well as liver weight and RG_30E and RG_50E improved glucose homeostasis, as indicated by fasting blood glucose levels and glucose tolerance. Hepatic triglyceride and total cholesterol levels were significantly decreased in db/db mice fed RG_30E and RG_50E. The antioxidant capacity of RG_30E and RG_50E was confirmed by a decrease in malondialdehyde levels and an increase in hepatic superoxide dismutase activity. The expression of genes related to glycolysis and gluconeogenesis was significantly regulated by RG_30E and RG_50E. These results suggest that fermented rice germ extracts have the potential to regulate hypoglycemia and hepatic glucose metabolism in type 2 diabetes db/db mice.

Sign in / Sign up

Export Citation Format

Share Document