Resveratrol long-term treatment differentiates INS-1E beta-cell towards improved glucose response and insulin secretion
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The clonal INS-1E beta-cell line has proven to be instrumental for numerous studies investigating the mechanisms of glucose-stimulated insulin secretion. The composition of its culture medium has not changed over the years, although some compounds have been recently highlighted for their effects on tissue differentiation. The present study investigated the effects of long-term treatment of INS-1E cells with 1 μM resveratrol on glucose-stimulated insulin secretion, testing an extended glucose dose response. The data demonstrate that chronic exposure to low-dose resveratrol expands the range of the glucose dose response of INS-1E cells beyond 15 mM glucose. We also assessed whether such beneficial effects could be retained after resveratrol withdrawal from the culture medium. This was not the case as INS-1E cells deprived of resveratrol returned to the phenotype of naïve cells, i.e., exhibiting a plateau phase at 15 mM glucose. Of note, although resveratrol has antioxidant properties, it cannot substitute for β-mercaptoethanol normally present in the medium of INS-1E cells as a reducing agent. In conclusion, the addition of resveratrol as a standard component of the culture medium of INS-1E cells improves glucose-stimulated insulin secretion.
KeywordsPancreatic beta-cell Insulin secretion Resveratrol INS-1E cells
The authors thank Thierry Brun and Laurène Vetterli for fruitful discussions and Clarissa Bartley for analysis of AMPK.
This work was supported by the State of Geneva and the Swiss National Science Foundation [146984 and 166625 to P.M.].
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342CrossRefGoogle Scholar
- 9.Efanov AM, Zaitsev SV, Mest HJ, Raap A, Appelskog IB, Larsson O, Berggren PO, Efendic S (2001) The novel imidazoline compound BL11282 potentiates glucose-induced insulin secretion in pancreatic beta-cells in the absence of modulation of K(ATP) channel activity. Diabetes 50:797–802CrossRefGoogle Scholar
- 10.Fiori JL, Shin YK, Kim W, Krzysik-Walker SM, Gonzalez-Mariscal I, Carlson OD, Sanghvi M, Moaddel R, Farhang K, Gadkaree SK, Doyle ME, Pearson KJ, Mattison JA, de Cabo R, Egan JM (2013) Resveratrol prevents beta-cell dedifferentiation in nonhuman primates given a high-fat/high-sugar diet. Diabetes 62:3500–3513CrossRefGoogle Scholar
- 14.Ishihara H, Asano T, Tsukuda K, Katagiri H, Inukai K, Anai M, Kikuchi M, Yazaki Y, Miyazaki JI, Oka Y (1993) Pancreatic beta cell line MIN6 exhibits characteristics of glucose metabolism and glucose-stimulated insulin secretion similar to those of normal islets. Diabetologia 36:1139–1145CrossRefGoogle Scholar
- 15.Jakab M, Lach S, Bacova Z, Langeluddecke C, Strbak V, Schmidt S, Iglseder E, Paulmichl M, Geibel J, Ritter M (2008) Resveratrol inhibits electrical activity and insulin release from insulinoma cells by block of voltage-gated Ca+ channels and swelling-dependent Cl- currents. Cell Physiol Biochem 22:567–578CrossRefGoogle Scholar
- 24.Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, Hubbard BP, Varela AT, Davis JG, Varamini B, Hafner A, Moaddel R, Rolo AP, Coppari R, Palmeira CM, de Cabo R, Baur JA, Sinclair DA (2012) dasSIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15:675–690CrossRefGoogle Scholar