scholarly journals Insulin Secretion with the Effect of Loureirin B through KATP Channel–Dependent Pathway

Author(s):  
Yijie Sha ◽  
Yuelin Zhang ◽  
Jing Cao ◽  
Kai Qian ◽  
Bing Niu ◽  
...  

The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For understanding the mechanism, a series of experiments had been employed based on computational methods and cell experiments. The insulin secretion significantly increased with the incubation of 0.01μM loureirin B for 4 hours. The viability of Ins-1 cells showed no significant difference with the treatment of loureirin B. Through computational methods, we hypothesized that loureirin B could interacts with KATP channels to promote insulin secretion. In cell experiments, it could be found that the current of KATP channel of Ins-1 cells was inhibited by the effect of loureirin B. After then, the voltage-dependent calcium channels were activated, the increase of Cx43 protein expression might mediate the Ca2+ to the intracellular. In summary, it could be concluded that loureirin B promoted insulin secretion mainly through inhibiting KATP current, the influx of Ca2+ to the Intracellular and the expression of Cx43.

1996 ◽  
Vol 271 (3) ◽  
pp. C804-C809 ◽  
Author(s):  
S. el Razi Neto ◽  
T. M. Zorn ◽  
R. Curi ◽  
A. R. Carpinelli

Previous study has shown that insulin secretion in response to a glucose stimulus (16.7 mM) is reduced in islets isolated from Walker 256 tumor-bearing rats compared with controls. The ultrastructure, 45Ca2+ and 86Rb+ fractional outflow rate, phosphoinositide hydrolysis, and [U-14C]glucose decarboxylation were examined in islets isolated from tumor-bearing and control rats. The general morphological features of the islets from the control and experimental groups were very similar. The 86Rb+ fractional outflow rate was not changed, whereas the 45Ca2+ fractional outflow rate, [U-14C]glucose decarboxylation, and phosphoinositide metabolism were markedly reduced in islets from tumor-bearing rats. The changes in 45Ca2+ fractional outflow rate in islets from tumor-bearing rats were not due to impaired functioning of voltage-dependent calcium channels. By perifusing the islets in the presence of high potassium concentration, evidence was obtained that phospholipase C from islets from tumor-bearing rats reduced response to calcium. To further examine the mechanism involved in the impairment of insulin secretion by islets from tumor-bearing rats, islets isolated from normal rats were perifused after preincubation in the presence of serum from tumor-bearing rats. The results suggest that a thermolabile circulating factor is partially responsible for the changes described in islets isolated from Walker 256 tumor-bearing rats.


2007 ◽  
Vol 293 (4) ◽  
pp. E901-E907 ◽  
Author(s):  
Tomasz Szkudelski

Resveratrol is a stilbene present in different plant species and exerting numerous beneficial effects, including prevention of diabetes and attenuation of some diabetic complications. Its inhibitory effect on insulin secretion was recently documented, but the exact mechanism underlying this action remains unknown. Experiments employing diazoxide and a high concentration of K+revealed that, in depolarized pancreatic islets incubated for 90 min with resveratrol (1, 10, and 100 μM), insulin secretion stimulated by glucose and leucine was impaired. The attenuation of the insulin secretory response to 6.7 mM glucose was not abrogated by blockade of intracellular estrogen receptors and was found to be accompanied by diminished islet glucose oxidation, enhanced lactate production, and reduced ATP levels. Glucose-induced hyperpolarization of the mitochondrial membrane was also reduced in the presence of resveratrol. Moreover, in depolarized islets incubated with 2.8 mM glucose, activation of protein kinase C or protein kinase A potentiated insulin release; however, under these conditions, resveratrol was ineffective. Further studies also revealed that, under conditions of blocked voltage-dependent calcium channels, the stilbene reduced insulin secretion induced by a combination of glucose with forskolin. These data demonstrate that resveratrol 1) inhibits the amplifying pathway of insulin secretion, 2) exerts an insulin-suppressive effect independently of its estrogenic/anti-estrogenic activity, 3) shifts islet glucose metabolism from mitochondrial oxidation to anaerobic, 4) fails to abrogate insulin release promoted without metabolic events, and 5) does not suppress hormone secretion as a result of the direct inhibition of Ca2+influx through voltage-dependent calcium channels.


2020 ◽  
Vol 598 (21) ◽  
pp. 4887-4905 ◽  
Author(s):  
Matthew T. Dickerson ◽  
Prasanna K. Dadi ◽  
Regan B. Butterworth ◽  
Arya Y. Nakhe ◽  
Sarah M. Graff ◽  
...  

2002 ◽  
Vol 283 (2) ◽  
pp. E207-E216 ◽  
Author(s):  
H. Huopio ◽  
S.-L. Shyng ◽  
T. Otonkoski ◽  
C. G. Nichols

ATP-sensitive potassium (KATP) channels are inhibited by intracellular ATP and activated by ADP. Nutrient oxidation in β-cells leads to a rise in [ATP]-to-[ADP] ratios, which in turn leads to reduced KATP channel activity, depolarization, voltage-dependent Ca2+ channel activation, Ca2+ entry, and exocytosis. Persistent hyperinsulinemic hypoglycemia of infancy (HI) is a genetic disorder characterized by dysregulated insulin secretion and, although rare, causes severe mental retardation and epilepsy if left untreated. The last five or six years have seen rapid advance in understanding the molecular basis of KATP channel activity and the molecular genetics of HI. In the majority of cases for which a genotype has been uncovered, causal HI mutations are found in one or the other of the two genes, SUR1 and Kir6.2, that encode the KATP channel. This article will review studies that have defined the link between channel activity and defective insulin release and will consider implications for future understanding of the mechanisms of control of insulin secretion in normal and diseased states.


2017 ◽  
Vol 4 (1) ◽  
pp. 16-23
Author(s):  
Suntoro ◽  
Ressi Susanti ◽  
Robiyanto

Diabetes mellitus is a metabolic disease with characteristics of hyperglycemia. Conventional treatments using oral medications such as glibenclamide and metformin have many side effects. Therefore, it is necessary to find an alternative drug that is more effective and safer. Some agents that are often used as anantihiperglikemia are cucumber and tomato.The purpose of this study was to determine the effectiveness of combination of cucumber and tomato juice to decrease blood glucose levels of male Wistar ratsusingglucose tolerance method. Male Wistar rats were fasted for 10 hours and then measured the levels of fasting blood glucose. Then animals test were given the juice (single and combination), 30 minutes later were given a dose of sucrose load of 6.75 g / KgBW orally. Blood glucose levels of animal testre-measured at 30th, 60th, 90th, and 120th minutes after loading sucrose using a glucometer.The measurement results showed that blood glucose levels of the combination of cucumber and tomato juice group with dose ratio of 28 g/KgBW:16.8 g/KgBW gave decrease blood glucose levels significantly compared to the negative control group (p≤0.05) and didn’t not provide a significant difference compared to the metformin group (p ≥0.05).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyun Sook Hwang ◽  
Mi Hyun Lee ◽  
Hyun Ah Kim

AbstractTonicity-responsive enhancer-binding protein (TonEBP; nuclear factor of activated T cells 5) is a transcription factor that responds to changes in osmolality. However, recent studies have shown that it also modulates immune responses under inflammatory conditions independently of hyperosmolality. Fibronectin fragments (FN-fs), which are abundant in the synovial fluid of patients with osteoarthritis (OA), induce expression of matrix metalloproteinases (MMPs) via the toll-like receptor-2 (TLR-2) signaling pathway. In this study we examined whether TonEBP is involved in 29-kDa FN-f-induced expression of MMPs. The expression of TonEBP was significantly higher in human osteoarthritis compared with normal cartilage samples. 29-kDa FN-f affected the expression of MMPs 1, 3, and 13 via TonEBP, and expression and nuclear accumulation of TonEBP were induced by activation of the phospholipase C/NF-κB/MAPK signaling pathway and, in particular, modulated by TLR-2. In addition, 29-kDa FN-f induced the expression of osmoregulatory genes, including Tau-T, SMIT, and AR, as well as voltage-dependent calcium channels via the TonEBP/TLR-2 signaling pathway. These results show that 29-kDa FN-f upregulates MMPs in chondrocytes via the TLR-2/TonEBP signaling pathway.


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