A novel long acting DPP-IV inhibitor PKF-275-055 stimulates β-cell proliferation resulting in improved glucose homeostasis in diabetic rats

2012 ◽  
Vol 83 (2) ◽  
pp. 241-252 ◽  
Author(s):  
Atul Sureshrao Akarte ◽  
B.P. Srinivasan ◽  
Sonia Gandhi
Keyword(s):  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Diabetic Rats ◽  
Β Cell ◽  
Dpp Iv ◽  
Long Acting

Tead1 Reciprocally Regulates Adult β-Cell Proliferation and Function to Maintain Glucose Homeostasis

2020 ◽  
Author(s):  
Jeongkyung Lee ◽  
Ruya Liu ◽  
Byung S. Kim ◽  
Yiqun Zhang ◽  
Feng Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Β Cell ◽  
And Function

scholarly journals GABA promotes β‐cell proliferation, but does not overcome impaired glucose homeostasis associated with diet‐induced obesity

2018 ◽  
Vol 33 (3) ◽  
pp. 3968-3984 ◽  
Author(s):  
Ashley Untereiner ◽  
Shaaban Abdo ◽  
Alpana Bhattacharjee ◽  
Himaben Gohil ◽  
Farzaneh Pourasgari ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Β Cell ◽  
Diet Induced Obesity

Neonatal growth and regeneration of β-cells are regulated by the Wnt/β-catenin signaling in normal and diabetic rats

2010 ◽  
Vol 298 (2) ◽  
pp. E245-E256 ◽  
Author(s):  
Florence Figeac ◽  
Benjamin Uzan ◽  
Monique Faro ◽  
Noura Chelali ◽  
Bernard Portha ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Pathway ◽  
Diabetic Rats ◽  
Β Cells ◽  
Β Cell ◽  
Ductal Cells ◽  
Gsk 3Β ◽  
Canonical Wnt

Wnt/β-catenin signaling is critical for a variety of fundamental cellular processes. Here, we investigated the implication of the Wnt/β-catenin signaling in the in vivo regulation of β-cell growth and regeneration in normal and diabetic rats. To this aim, TCF7L2, the distal effector of the canonical Wnt pathway, was knocked down in groups of normal and diabetic rats by the use of specific antisense morpholino-oligonucleotides. In other groups of diabetic rats, the Wnt/β-catenin pathway was activated by the inhibition of its negative regulator GSK-3β. GSK-3β was inactivated by either LiCl or anti-GSK-3β oligonucleotides. The β-cell mass was evaluated by morphometry. β-cell proliferation was assessed in vivo and in vitro by BrdU incorporation method. In vivo β-cell neogenesis was estimated by the evaluation of PDX1-positive ductal cells and GLUT2-positive ductal cells and the number of β cells budding from the ducts. We showed that the in vivo disruption of the canonical Wnt pathway resulted in the alteration of normal and compensatory growth of β-cells mainly through the inhibition of β-cell proliferation. Conversely, activation of the Wnt pathway through the inhibition of GSK-3β had a significant stimulatory effect on β-cell regeneration in diabetic rats. In vitro, GSK-3β inactivation resulted in the stimulation of β-cell proliferation. This was mediated by the stabilization of β-catenin and the induction of cyclin D. Taken together, our results demonstrate the involvement of the canonical Wnt signaling in the neonatal regulation of normal and regenerative growth of pancreatic β-cells. Moreover, we provide evidence that activation of this pathway by pharmacological maneuvers can efficiently improve β-cell regeneration in diabetic rats. These findings might have potential clinical applications in the regenerative therapy of diabetes.

Two drugs converged in a pancreatic β cell

2020 ◽  
Vol 12 (530) ◽  
pp. eaba7359
Author(s):  
Marissa A. Scavuzzo ◽  
Malgorzata Borowiak
Keyword(s):  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Receptor Agonist ◽  
Pancreatic Β Cell ◽  
Β Cell

Combining a DYRK1A inhibitor and GLP-1 receptor agonist boosts human pancreatic β cell proliferation and glucose homeostasis in vivo (Ackeifi et al., this issue).

Exercise improves glucose homeostasis that has been impaired by a high-fat diet by potentiating pancreatic β-cell function and mass through IRS2 in diabetic rats

2007 ◽  
Vol 103 (5) ◽  
pp. 1764-1771 ◽  
Author(s):  
Sunmin Park ◽  
Sang Mee Hong ◽  
Ji Eun Lee ◽  
So Ra Sung
Keyword(s):  
Cell Proliferation ◽  
High Fat Diet ◽  
Cell Function ◽  
Cell Mass ◽  
Diabetic Rats ◽  
Pancreatic Β Cell ◽  
High Fat ◽  
Β Cell ◽  
Igf I ◽  
Β Cell Function

In this study, we investigated the effects of a high-fat diet and exercise on pancreatic β-cell function and mass and its molecular mechanism in 90% pancreatectomized male rats. The pancreatectomized diabetic rats were given control diets (20% energy) or a high-fat (HF) diet (45% energy) for 12 wk. Half of each group was given regular exercise on an uphill treadmill at 20 m/min for 30 min 5 days/wk. HF diet lowered first-phase insulin secretion with glucose loading, whereas exercise training reversed this decrease. However, second-phase insulin secretion did not differ among the groups. Exercise increased pancreatic β-cell mass. This resulted from stimulated β-cell proliferation and reduced apoptosis, which is associated with potentiated insulin or IGF-I signaling through insulin receptor substrate-2 (IRS2) induction. Although the HF diet resulted in decreased proliferation and accelerated apoptosis by weakened insulin and IGF-I signaling from reduction of IRS2 protein, β-cell mass was maintained in HF rats just as much as in control rats via increased individual β-cell size and neogenesis from precursor cells. Consistent with the results of β-cell proliferation, pancreas duodenal homeobox-1 expression increased in the islets of rats in the exercise groups, and it was reduced the most in rats fed the HF diet. In conclusion, exercise combined with a moderate fat diet is a good way to maximize β-cell function and mass through IRS2 induction to alleviate the diabetic condition. This study suggests that dietary fat contents and exercise modulate β-cell function and mass to overcome insulin resistance in two different pathways.

scholarly journals Effects of 22 traditional anti-diabetic medicinal plants on DPP-IV enzyme activity and glucose homeostasis in high-fat fed obese diabetic rats

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Prawej Ansari ◽  
Mary P. Hannon-Fletcher ◽  
Peter R. Flatt ◽  
Yasser H.A. Abdel-Wahab
Keyword(s):  
Body Weight ◽  
Enzyme Activity ◽  
Medicinal Plants ◽  
Glucose Homeostasis ◽  
Diabetic Rats ◽  
Hot Water ◽  
High Fat ◽  
Dpp Iv ◽  
Obese Diabetic Rats

Abstract The present study investigated the effects of hot water extracts of 22 medicinal plants used traditionally to treat diabetes on Dipeptidyl peptidase-IV (DPP-IV) activity both in vitro and in vivo in high-fat fed (HFF) obese-diabetic rats. Fluorometric assay was employed to determine the DPP-IV activity. For in vivo studies, HFF obese-diabetic rats were fasted for 6 h and blood was sampled at different times before and after the oral administration of the glucose alone (18 mmol/kg body weight) or with either of the four most active plant extracts (250 mg/5 ml/kg, body weight) or established DPP-IV inhibitors (10 μmol/5 ml/kg). DPP-IV inhibitors: sitagliptin, vildagliptin and diprotin A, decreased enzyme activity by a maximum of 95–99% (P<0.001). Among the 22 natural anti-diabetic plants tested, AnogeissusLatifolia exhibited the most significant (P<0.001) inhibitory activity (96 ± 1%) with IC50 and IC25 values of 754 and 590 μg/ml. Maximum inhibitory effects of other extracts: Aegle marmelos, Mangifera indica, Chloropsis cochinchinensis, Trigonella foenum-graecum and Azadirachta indica were (44 ±7%; 38 ± 4%; 31±1%; 28±2%; 27±2%, respectively). A maximum of 45% inhibition was observed with >25 μM concentrations of selected phytochemicals (rutin). A.latifolia, A. marmelos, T. foenum-graecum and M. indica extracts improved glucose tolerance, insulin release, reduced DPP-IV activity and increased circulating active GLP-1 in HFF obese-diabetic rats (P<0.05–0.001). These results suggest that ingestion of selected natural anti-diabetic plants, in particular A. latifolia, A. marmelos, T. foenum-graecum and M. indica can substantially inhibit DPP-IV and improve glucose homeostasis, thereby providing a useful therapeutic approach for the treatment of T2DM.

scholarly journals Glucose homeostasis changes and pancreatic β-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus

2015 ◽  
Vol 35 (3) ◽  
pp. 264-272
Author(s):  
Ana Elena Rodríguez-Rodríguez ◽  
Javier Triñanes ◽  
Esteban Porrini ◽  
Silvia Velázquez-García ◽  
Cecilia Fumero ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Gαi/o-coupled receptor signaling restricts pancreatic β-cell expansion

2015 ◽  
Vol 112 (9) ◽  
pp. 2888-2893 ◽  
Author(s):  
Miles Berger ◽  
David W. Scheel ◽  
Hector Macias ◽  
Takeshi Miyatsuka ◽  
Hail Kim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Cell Mass ◽  
Perinatal Period ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Gpcr Signaling

Gi-GPCRs, G protein-coupled receptors that signal via Gα proteins of the i/o class (Gαi/o), acutely regulate cellular behaviors widely in mammalian tissues, but their impact on the development and growth of these tissues is less clear. For example, Gi-GPCRs acutely regulate insulin release from pancreatic β cells, and variants in genes encoding several Gi-GPCRs—including the α-2a adrenergic receptor, ADRA2A—increase the risk of type 2 diabetes mellitus. However, type 2 diabetes also is associated with reduced total β-cell mass, and the role of Gi-GPCRs in establishing β-cell mass is unknown. Therefore, we asked whether Gi-GPCR signaling regulates β-cell mass. Here we show that Gi-GPCRs limit the proliferation of the insulin-producing pancreatic β cells and especially their expansion during the critical perinatal period. Increased Gi-GPCR activity in perinatal β cells decreased β-cell proliferation, reduced adult β-cell mass, and impaired glucose homeostasis. In contrast, Gi-GPCR inhibition enhanced perinatal β-cell proliferation, increased adult β-cell mass, and improved glucose homeostasis. Transcriptome analysis detected the expression of multiple Gi-GPCRs in developing and adult β cells, and gene-deletion experiments identified ADRA2A as a key Gi-GPCR regulator of β-cell replication. These studies link Gi-GPCR signaling to β-cell mass and diabetes risk and identify it as a potential target for therapies to protect and increase β-cell mass in patients with diabetes.

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