Tocotrienols Stimulate Insulin Secretion of Rat Pancreatic Isolated Islets in a Dynamic Culture

被引:5
作者
Chia, Ling L. [1 ]
Jantan, Ibrahim [1 ]
Chua, Kien H. [2 ]
机构
[1] Univ Kebangsaan Malaysia, Drug & Herbal Res Ctr, Fac Pharm, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
[2] Univ Kebangsaan Malaysia, Dept Physiol, Fac Pharm, Jalan Yaacob Latif, Kuala Lumpur 56000, Malaysia
关键词
Tocotrienols; pancreatic islets; insulin secretion; microfluidic system; glucose; potassium chloride; CHANNEL-INDEPENDENT PATHWAY; TYPE-2; DIABETES-MELLITUS; INDUCED NEPHROPATHY; VITAMIN-E; IN-VITRO; GLUCOSE; TOCOPHEROLS; ANTIOXIDANT; CELLS; GLIBENCLAMIDE;
D O I
10.2174/1389201018666170808144703
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Tocotrienols (T3) are the naturally occurring vitamin E derivatives that possess antioxidant properties and therapeutic potential in diabetic complications. The bioactivities of the derivatives are determined by the number and arrangement of methyl substitution on the structure. Objective: The objective of this study was to determine the effects of T3 derivatives, delta-T3, gamma-T3 and alpha-T3 on insulin secretion of rat pancreatic islets in a dynamic culture. Method: Pancreatic islets isolated from male Wistar rats were treated with T3 for 1 h at 37 degrees C in a microfluidic system with continuous operation that provided a stable cell culture environment. Glucose (2.8 mM and 16.7 mM, as basal and stimulant, respectively) and potassium chloride (KCl) (30 mM) were added to the treatment in calcium free medium. The supernatant was collected for insulin measurements. Results: Short-term exposure (1 h) of delta-T3 to beta cells in the stimulant glucose condition significantly potentiated insulin secretion in a dose-dependent manner. gamma-T3 and alpha-T3 also displayed dose-dependent effect but were less effective in the activation of insulin secretion. Essentially, KCl, a pancreatic beta cell membrane depolarizing agent, added into the treatment further enhanced the insulin secretion of delta-T3, gamma-T3 and alpha-T3 with ED50 values of 504, 511 and 588 mu M, respectively. Conclusion: The findings suggest the potential of delta-T3 in regulating glucose-stimulated insulin secretion (GSIS) in response to the intracellular calcium especially in the presence of KCl.
引用
收藏
页码:560 / 568
页数:9
相关论文
共 49 条
[1]   Tocotrienols, the vitamin E of the 21st century: Its potential against cancer and other chronic diseases [J].
Aggarwal, Bharat B. ;
Sundaram, Chitra ;
Prasad, Seema ;
Kannappan, Ramaswamy .
BIOCHEMICAL PHARMACOLOGY, 2010, 80 (11) :1613-1631
[2]   CALCIUM-INDEPENDENT POTENTIATION OF INSULIN RELEASE BY CYCLIC-AMP IN SINGLE BETA-CELLS [J].
AMMALA, C ;
ASHCROFT, FM ;
RORSMAN, P .
NATURE, 1993, 363 (6427) :356-358
[3]   Tocopherols and tocotrienols in membranes: A critical review [J].
Atkinson, Jeffrey ;
Epand, Raquel F. ;
Epand, Richard M. .
FREE RADICAL BIOLOGY AND MEDICINE, 2008, 44 (05) :739-764
[4]   The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia [J].
Baliarsingh, S ;
Beg, ZH ;
Ahmad, J .
ATHEROSCLEROSIS, 2005, 182 (02) :367-374
[5]   Metformin for the treatment of polycystic ovary syndrome [J].
Barbieri, RL .
OBSTETRICS AND GYNECOLOGY, 2003, 101 (04) :785-793
[6]   Engineering cellular microenvironments to cell-based drug testing improve [J].
Bhadriraju, K ;
Chen, CS .
DRUG DISCOVERY TODAY, 2002, 7 (11) :612-620
[7]  
CHARLES MA, 1975, J BIOL CHEM, V250, P6134
[8]   Effects of Tocotrienols on Insulin Secretion-Associated Genes Expression of Rat Pancreatic Islets in a Dynamic Culture [J].
Chia, Ling L. ;
Jantan, Ibrahim ;
Chua, Kien H. ;
Lem, Kok W. ;
Rullah, Kama ;
Aluwi, Mohd F. M. .
FRONTIERS IN PHARMACOLOGY, 2016, 7
[9]   Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events):: a randomised controlled trial [J].
Dormandy, JA ;
Charbonnel, B ;
Eckland, DJA ;
Erdmann, E ;
Massi-Benedetti, M ;
Kmoules, IK ;
Skene, AM ;
Tan, MH ;
Lefébvre, PJ ;
Murray, GD ;
Standl, E ;
Wilcox, RG ;
Wlhelmsen, L ;
Betteridge, J ;
Birkeland, K ;
Golay, A ;
Heine, RJ ;
Korányi, L ;
Laakso, M ;
Mokán, M ;
Norkus, A ;
Pirags, V ;
Podar, T ;
Scheen, A ;
Scherbaum, W ;
Schernthaner, G ;
Schmitz, O ;
Skrha, J ;
Smith, U ;
Taton, J .
LANCET, 2005, 366 (9493) :1279-1289
[10]   CONTROL OF SECRETION VESICLE MARGINATION AND LYSIS BY GLUCOSE, IBMX, AND GLYBURIDE [J].
DRAZNIN, B ;
STEINBERG, JP ;
GOODMAN, M ;
LEITNER, JW ;
SUSSMAN, KE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1985, 248 (03) :E375-E380