scholarly journals Differential Activation of Protein Kinase B and p70S6Kby Glucose and Insulin-like Growth Factor 1 in Pancreatic β-Cells (INS-1)

2001 ◽  
Vol 276 (24) ◽  
pp. 21110-21120 ◽  
Author(s):  
Lorna M. Dickson ◽  
Melissa K. Lingohr ◽  
Jill McCuaig ◽  
Sigrun R. Hügl ◽  
Lynn Snow ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Insulin Like Growth Factor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Differential Activation

Protein Kinase B Is Expressed in Pancreatic β Cells and Activated upon Stimulation with Insulin-like Growth Factor I

1998 ◽  
Vol 250 (1) ◽  
pp. 181-186 ◽  
Author(s):  
Lena Stenson Holst ◽  
Hindrik Mulder ◽  
Vincent Manganiello ◽  
Frank Sundler ◽  
Bo Ahrén ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Insulin Like Growth Factor ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Factor I ◽  
Growth Factor I

scholarly journals Vitamin D3 Activates Phosphatidylinositol-3-Kinase/Protein Kinase B via Insulin-Like Growth Factor-1 to Improve Testicular Function in Diabetic Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yanyan He ◽  
Yang Liu ◽  
Qing-Zhu Wang ◽  
Feng Guo ◽  
Fengjuan Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Diabetic Rats ◽  
Testicular Function ◽  
Insulin Like Growth Factor ◽  
Wild Type ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Objective. In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. Materials and Methods. Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 μg/kg/day), high (0.1 μg/kg/day), and high (0.1 μg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 μg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. Results. Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. Conclusions. The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.

scholarly journals Protein Kinase B/Akt Prevents Fatty Acid-induced Apoptosis in Pancreatic β-Cells (INS-1)

2002 ◽  
Vol 277 (51) ◽  
pp. 49676-49684 ◽  
Author(s):  
Christian E. Wrede ◽  
Lorna M. Dickson ◽  
Melissa K. Lingohr ◽  
Isabelle Briaud ◽  
Christopher J. Rhodes
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Cell Apoptosis ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Glycogen Synthase Kinase ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Induced Apoptosis

Free fatty acids (FFA) have been reported to reduce pancreatic β-cell mitogenesis and to increase apoptosis. Here we show that the FFA, oleic acid, increased apoptosis 16-fold in the pancreatic β-cell line, INS-1, over a 18-h period as assessed by Hoechst 33342/propidium iodide staining and caspase-3 and -9 activation, with negligible necrosis. A parallel analysis of the phosphorylation activation of protein kinase B (PKB) showed this was reduced in the presence of FFA that correlated with the incidence of apoptosis. At stimulatory 15 mmglucose and/or in the added presence of insulin-like growth factor 1, FFA-induced β-cell apoptosis was lessened compared with that at a basal 5 mmglucose. However, most strikingly, adenoviral mediated expression of a constitutively active PKB, but not a “kinase-dead” PKB variant, essentially prevented FFA-induced β-cell apoptosis under all glucose/insulin-like growth factor 1 conditions. Further analysis of pro-apoptotic downstream targets of PKB, implicated a role for PKB-mediated phosphorylation inhibition of glycogen synthase kinase-3α/β and the forkhead transcription factor, FoxO1, in protection of FFA-induced β-cell apoptosis. In addition, down-regulation of the pro-apoptotic tumor suppresser protein, p53, via PKB-mediated phosphorylation of MDM2 might also play a role in partially protecting β-cells from FFA-induced apoptosis. Adenoviral mediated expression of wild type p53 potentiated FFA-induced β-cell apoptosis, whereas expression of a dominant negative p53 partly inhibited β-cell apoptosis by ∼50%. Hence, these data demonstrate that PKB activation plays an important role in promoting pancreatic β-cell survival in part via inhibition of the pro-apoptotic proteins glycogen synthase kinase-3α/β, FoxO1, and p53. This, in turn, provides novel insight into the mechanisms involved in FFA-induced β-cell apoptosis.

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