Streptozotocin-induced β-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain

Nikolakopoulou, Polyxeni; Chatzigeorgiou, Antonios; Kourtzelis, Ioannis; Toutouna, Louiza; Masjkur, Jimmy; Arps-Forker, Carina; Poser, Steven; Rozman, Jan; Rathkolb, Birgit; Aguilar-Pimentel, Antonio; Wolf, Eckhard; Ollert, Markus; Schmidt‐Weber, Carsten B.; Fuchs, Helmut; Gailus‐Durner, Valérie; Angelis, Martin Hrabě de; Tsata, Vasiliki; Monasor, Laura Sebastián; Troullinaki, Maria; Witt, Anke; Anastasiou, Vivian; Chrousos, George P.; Yi, Chun-Xia; García‐Cáceres, Cristina; Tschöp, Matthias H.; Bornstein, Stefan R.; Androutsellis-Theotokis, Andreas

doi:10.1038/s41598-018-29434-2

Cited by 6 publications

(3 citation statements)

References 88 publications

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“…Immunofluorescence Analysis of Insulin in the Pancreatic β-Cell of T2DM Mice. Since the previous study reported that insulin is secreted by β-cells in the pancreas, which is one of the most important metabolic hormones to control blood glucose, 38,39 we investigated the ability of insulin secretion and the potential effects of MTNP on pancreatic βcell injury in diabetic mice. Immunofluorescence (IF) analysis was utilized to measure the expression of insulin in the pancreas, in which the anti-insulin antibody was used to determine the insulin expression.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Fan

Zhang

Zhao

et al. 2022

ACS Appl. Mater. Interfaces

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Tea polysaccharide (TPS) is a bioactive compound that has attracted increasing attention for its health effect on regulating the metabolism of glucose and lipid. Moreover, due to their good biocompatibility and biodegradability, TPS-based nanoparticles have emerged as effective nanocarriers for the delivery of bioactive molecules. In this study, we developed a TPS-based biocarrier system for the orally targeted administration of Mn(II) ions and investigated their antidiabetic effects in C57BL/6 mice with HFD/streptozotocin (STZ)-induced T2DM. Mn(II)-loaded TPS-based nanoparticles (MTNPs) were synthesized, in which negatively charged functional groups in protein and uronic acid in TPS conjugates would act as binding sites for Mn(II) ions, which is responsible for the cross-linking reaction of MTNP. The resulting MTNP had a spherical shape and a mean particle size of around 30 nm with a Mn(II) ion content of 2.24 ± 0.13 mg/g. In T2DM mice, we discovered that MTNP treatment significantly lowered blood glucose levels and improved glucose intolerance. Furthermore, the impact of MTNP on the recovery of FINS, the homeostatic index of insulin resistance (HOMA-IR), and the homeostatic index of β-cell (HOMA β-cell) levels was significantly larger (p < 0.05) than TPS alone, demonstrating that Mn(II) ions can enhance TPS's ability to repair HFD/STZ-induced β-cell damage. Mn(II) ions in MTNP not only acted as cofactors to increase the exocytosis of insulin secretory cells by upregulating the expression of Ca(II)/calmodulin-dependent protein kinase II (CaMK II) but also promoted TPS's lipid-lowering effect in T2DM mice by inhibiting glucogenesis and regulating the lipid metabolism. Our findings suggest that Mn(II) ions can be used not only as cross-linkers in the formation of nanoparticulated TPS but also as cofactors in improving the functional role of TPS in regulating the glucose and lipid metabolism, which will provide insights into the development of TPS-based drug delivery systems for the prevention of type 2 diabetes.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Fan

Zhang

Zhao

et al. 2022

ACS Appl. Mater. Interfaces

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“…Streptozotocin and alloxan administration can induce hyperglycemia by increasing β-cell death in non-obese rats. However, their administration increases β-cell death through elevated reactive oxygen species, removal of which can reduce diabetic severity during treatment [ 36 , 37 ]. They also induce neuronal cell death [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Aqueous Blackcurrant Extract Improves Insulin Sensitivity and Secretion and Modulates the Gut Microbiome in Non-Obese Type 2 Diabetic Rats

Yang

Zhang

et al. 2021

Antioxidants

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This study was undertaken to determine whether aqueous blackcurrant extracts (BC) improve glucose metabolism and gut microbiomes in non-obese type 2 diabetic animals fed a high-fat diet and to identify the mechanism involved. Partially pancreatectomized male Sprague–Dawley rats were provided a high-fat diet containing 0% (control), 0.2% (L-BC; low dosage), 0.6% (M-BC; medium dosage), and 1.8% (H-BC; high dosage) blackcurrant extracts; 0.2% metformin (positive-C); plus 1.8%, 1.6%, 1.2%, 0%, and 1.6% dextrin, specifically indigestible dextrin, daily for 8 weeks. Daily blackcurrant extract intakes were equivalent to 100, 300, and 900 mg/kg body weight (bw). After a 2 g glucose or maltose/kg bw challenge, serum glucose and insulin concentrations during peak and final states were obviously lower in the M-BC and H-BC groups than in the control group (p < 0.05). Intraperitoneal insulin tolerance testing showed that M-BC and H-BC improved insulin resistance. Hepatic triglyceride deposition, TNF-α expression, and malondialdehyde contents were lower in the M-BC and H-BC groups than in the control group. Improvements in insulin resistance in the M-BC and H-BC groups were associated with reduced inflammation and oxidative stress (p < 0.05). Hyperglycemic clamp testing showed that insulin secretion capacity increased in the acute phase (2 to 10 min) in the M-BC and H-BC groups and that insulin sensitivity in the hyperglycemic state was greater in these groups than in the control group (p < 0.05). Pancreatic β-cell mass was greater in the M-BC, H-BC, and positive-C groups than in the control group. Furthermore, β-cell proliferation appeared to be elevated and apoptosis was suppressed in these three groups (p < 0.05). Serum propionate and butyrate concentrations were higher in the M-BC and H-BC groups than in the control group. BC dose-dependently increased α-diversity of the gut microbiota and predicted the enhancement of oxidative phosphorylation-related microbiome genes and downregulation of carbohydrate digestion and absorption-related genes, as determined by PICRUSt2 analysis. In conclusion, BC enhanced insulin sensitivity and glucose-stimulated insulin secretion, which improved glucose homeostasis, and these improvements were associated with an incremental increase of the α-diversity of gut microbiota and suppressed inflammation and oxidative stress.

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“…affects hepcidin level that depends on peripheral insulin resistance rather than decrease in insulin secretion. [24][25][26] Hepcidin, a hormone that inhibits the absorption of iron from the intestine, may show increased levels in T2DM patients due to the increase of insulin secretion stimulated by the high level of blood glucose. 27 In addition, high hepcidin level may have resulted from the stimulation of the extrahepatic pathway, specifically from macrophages, as a result of inflammatory process induction.…”

Section: Conflict Of Interestmentioning

confidence: 99%

Tracking hepcidin level in induced type 2 diabetic rats and how Empagliflozin affects its level

Ali

Ahmed

Ibrahim

et al. 2022

JPTCP

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Background: Hepcidin is a hormone that contributes to iron homeostasis, produced either through hepatic or extrahepatic pathways. Its production may be affected by proinflammatory mediators released by macrophages, which play a role in the development of peripheral insulin resistance. Insulin itself may increase the production of hepcidin hormone from pancreatic β-cells. Objectives: To evaluate the impact of induction of type 2 diabetes mellitus (T2DM) in albino wister rats on the level of hepcidin. Also, to examine the role of 2-week use of Empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2 Inhibitor), on the hepcidin level comparing to control. Method: An interventional study includes randomization of 36 rats into three groups (A: negative control, B: positive control, and C: Empagliflozin group). Two rats were excluded from the study for different reasons. T2DM was induced using high-fat diet/high-sugar diet (HFD/HSD) for 8 weeks. Empagliflozin was then given to Group C for 2 weeks at a dose of 35 mg/kg/day. Hepcidin level was determined at the Tracking hepcidin level e159

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Streptozotocin-induced β-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain

Cited by 6 publications

References 88 publications

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Aqueous Blackcurrant Extract Improves Insulin Sensitivity and Secretion and Modulates the Gut Microbiome in Non-Obese Type 2 Diabetic Rats

Tracking hepcidin level in induced type 2 diabetic rats and how Empagliflozin affects its level

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