Low glibenclamide concentrations affect endoplasmic reticulum stress in INS-1 cells under glucotoxic or glucolipotoxic conditions

다국어 초록 (Multilingual Abstract)

Background/Aims: β-Cell apoptosis caused by increased endoplasmic reticulum (ER) stress is an important pathogenic component of type 2 diabetes mellitus.
In theory, sulfonylureas, used for the treatment of diabetes, can contribute to ER stress. We assessed changes in ER stress in pancreatic β-cells under glucotoxic or glucolipotoxic conditions using low concentrations of the sulfonylurea, glibenclamide (GB).
Methods: Low concentrations of GB (10 or 100 nM) were added to INS-1 cells cultured under glucotoxic or glucolipotoxic conditions. The degree of viability, level of apoptosis and levels of markers associated with ER stress were measured.
Results: Apoptosis decreased in response to low concentrations of GB under glucolipotoxic but not glucotoxic conditions. Most ER stress markers decreased upon the addition of GB. Under glucotoxic conditions, changes in the levels of ER stress markers were not consistent. However, all decreased significantly under glucolipotoxic conditions.
Conclusions: Low concentrations of GB exerted antiapoptotic effects through the attenuation of ER stress under glucolipotoxic conditions.

참고문헌 (Reference)

1 Kaufman RJ, "The unfolded protein response in nutrient sensing and differentiation" 3 : 411-421, 2002

2 Eizirik DL, "The role for endoplasmic reticulum stress in diabetes mellitus" 29 : 42-61, 2008

3 Marchetti P, "The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients" 50 : 2486-2494, 2007

4 Oslowski CM, "The binary switch between life and death of endoplasmic reticulum-stressed beta cells" 17 : 107-112, 2010

5 Rutkowski DT, "That which does not kill me makes me stronger: adapting to chronic ER stress" 32 : 469-476, 2007

6 Maedler K, "Sulfonylurea induced beta-cell apoptosis in cultured human islets" 90 : 501-506, 2005

7 Takahashi A, "Sulfonylurea and glinide reduce insulin content, functional expression of K(ATP) channels, and accelerate apoptotic beta-cell death in the chronic phase" 77 : 343-350, 2007

8 Ron D, "Signal integration in the endoplasmic reticulum unfolded protein response" 8 : 519-529, 2007

9 El-Assaad W, "Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death" 144 : 4154-4163, 2003

10 Rhodes CJ., "Processing of the insulin molecule, In Diabetes Mellitus: A Fundamental and Clinical Text. 3rd ed" Lippincott Williams & Wilkins 27-50, 2004

11 Poitout V, "Minireview: secondary betacell failure in type 2 diabetes: a convergence of glucotoxicity and lipotoxicity" 143 : 339-342, 2002

12 Zhou YP, "Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans" 80 : 1584-1590, 1995

13 Cnop M, "Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation" 50 : 1771-1777, 2001

14 UK Prospective Diabetes Study (UKPDS) Group, "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)" 352 : 837-853, 1998

15 Huang CJ, "High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress mediated beta-cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes" 56 : 2016-2027, 2007

16 Kahn SE, "Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy" 355 : 2427-2443, 2005

17 Ritz-Laser B, "Glucose-induced preproinsulin gene expression is inhibited by the free fatty acid palmitate" 140 : 4005-4014, 1999

18 Efanova IB, "Glucose and tolbutamide induce apoptosis in pancreatic beta-cell: a process dependent on intracellular Ca2+ concentration" 273 : 33501-33507, 1998

19 Shimabukuro M, "Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes" 95 : 2498-2502, 1998

20 Qian L, "Endoplasmic reticulum stress in beta cells: latent mechanism of secondary sulfonylurea failure in type 2 diabetes?" 71 : 889-891, 2008

21 Laybutt DR, "Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes" 50 : 752-763, 2007

22 Del Guerra S, "Effects of prolonged in vitro exposure to sulphonylureas on the function and survival of human islets" 19 : 60-64, 2005

23 Bertolotti A, "Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response" 2 : 326-332, 2000

24 Maedler K, "Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function" 50 : 69-76, 2001

25 Urano F, "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1" 287 : 664-666, 2000

26 Shen X, "Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development" 107 : 893-903, 2001

27 Jaber LA, "Comparison of pharmacokinetics and pharmacodynamics of short- and long-term glyburide therapy in NIDDM" 17 : 1300-1306, 1994

28 Elks ML., "Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release" 133 : 208-214, 1993

29 Chang-Chen KJ, "Betacell failure as a complication of diabetes" 9 : 329-343, 2008

30 Maundrell K, "Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/ stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Rac1" 272 : 25238-25242, 1997

31 Price J, "Akt-1 mediates survival of chondrocytes from endoplasmic reticulum-induced stress" 222 : 502-508, 2010

32 Nishitoh H, "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats" 16 : 1345-1355, 2002

33 Ishigaki S, "AATF mediates an antiapoptotic effect of the unfolded protein response through transcriptional regulation of AKT1" 17 : 774-786, 2010

34 Yoshida H, "A time-dependent phase shift in the mammalian unfolded protein response" 4 : 265-271, 2003